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Homoharringtonine (Omacetaxine Mepesuccinate) in Treating Patients With Chronic Myeloid Leukemia (CML) With the T315I BCR-ABL Gene Mutation

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ClinicalTrials.gov Identifier: NCT00375219
Recruitment Status : Completed
First Posted : September 12, 2006
Results First Posted : June 3, 2014
Last Update Posted : June 3, 2014
Sponsor:
Collaborators:
Cephalon
ChemGenex Pharmaceuticals
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products R&D, Inc. )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Myeloid Leukemia
Intervention Drug: Omacetaxine mepesuccinate
Enrollment 103
Recruitment Details  
Pre-assignment Details  
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase
Hide Arm/Group Description Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years. Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years. Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Period Title: Overall Study
Started 62 20 21
Completed 3 0 0
Not Completed 59 20 21
Reason Not Completed
Failure to achieve a response             16             2             0
Adverse Event             8             2             1
Protocol Violation             1             0             1
Request of Patient, PI, Sponsor or RA             5             3             0
Lost to Follow-up             1             1             0
Disease progression             18             9             12
Death             4             3             7
Hematologic resistance             1             0             0
Specific tyrosine kinase inhibitor avail             1             0             0
Allograft             2             0             0
Cord blood transplantation             1             0             0
Withdrawal by Subject             1             0             0
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total
Hide Arm/Group Description Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years. Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years. Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years. Total of all reporting groups
Overall Number of Baseline Participants 62 20 21 103
Hide Baseline Analysis Population Description
Intent to treat population includes all participants who provide written informed consent and receive at least one dose of study medication.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 62 participants 20 participants 21 participants 103 participants
59
(26 to 83)
59
(30 to 83)
50
(19 to 64)
57
(19 to 83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 62 participants 20 participants 21 participants 103 participants
Female
20
  32.3%
5
  25.0%
7
  33.3%
32
  31.1%
Male
42
  67.7%
15
  75.0%
14
  66.7%
71
  68.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 62 participants 20 participants 21 participants 103 participants
Caucasian 48 12 13 73
Black 4 6 6 16
Hispanic 0 0 0 0
Asian 8 2 2 12
Other 2 0 0 2
Height  
Median (Full Range)
Unit of measure:  Centimeter
Number Analyzed 62 participants 20 participants 21 participants 103 participants
171.5
(146.0 to 192.0)
172.0
(155.0 to 185.0)
170.2
(157.0 to 196.0)
171.0
(146.0 to 196.0)
Weight  
Median (Full Range)
Unit of measure:  Kilograms
Number Analyzed 62 participants 20 participants 21 participants 103 participants
77.7
(34.0 to 115.0)
69.1
(40.0 to 118.8)
68.8
(43.0 to 117.7)
76.0
(34.0 to 118.8)
Body Surface Area (BSA)  
Median (Full Range)
Unit of measure:  Meters^2
Number Analyzed 62 participants 20 participants 21 participants 103 participants
1.9
(1.2 to 2.3)
1.8
(1.3 to 2.3)
1.8
(1.4 to 2.4)
1.9
(1.2 to 2.4)
New York Heart Association (NYHA) Classification   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 62 participants 20 participants 21 participants 103 participants
Class I 61 18 18 97
Class II 1 2 3 6
Class III 0 0 0 0
Class IV 0 0 0 0
[1]
Measure Description:
  • Class I: Cardiac disease, but no symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc.
  • Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.
  • Class III: Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m). Comfortable only at rest.
  • Class IV: Severe limitations. Experiences symptoms even while at rest. Mostly bed-bound patients.
Eastern Cooperative Oncology Group Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 62 participants 20 participants 21 participants 103 participants
Grade 0 41 6 6 53
Grade 1 20 11 9 40
Grade 2 1 2 5 8
Grade 3 0 1 1 2
[1]
Measure Description:
  • Grade 0: Fully active, able to carry on all pre-disease activities without restriction;
  • Grade 1: Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature;
  • Grade 2: Ambulatory and capable of all self-care but unable to work. Up and about more than 50% of waking hours;
  • Grade 3: Capable of only limited self-care, confined to bed or chair > 50% of waking hours;
  • Grade 4: Completely disabled. Cannot carry on any self-care. Confined to bed or chair.
Time from Initial Chronic Myeloid Leukemia (CML) Diagnosis  
Median (Full Range)
Unit of measure:  Months
Number Analyzed 62 participants 20 participants 21 participants 103 participants
50.0
(10.9 to 234.3)
98.0
(34.3 to 285.6)
46.6
(5.2 to 139.8)
59.6
(5.2 to 285.6)
1.Primary Outcome
Title Percentage of Participants Achieving an Overall Hematologic Response by Subpopulation and Total Population
Hide Description

Subpopulations reflect chronic myeloid leukemia (CML) phases at the time of enrollment: chronic, accelerated, and blast phase. Primary endpoints as adjudicated by the Data Monitoring Committee were used for the primary analyses.

Overall hematologic response for chronic phase participants includes confirmed complete hematologic response (CHR). Overall hematologic response for accelerated or blast phase participants includes confirmed complete hematologic response (CHR), no evidence of leukemia (NEL), or return to chronic phase (RCP). Hematologic response must last >= 8 weeks to be considered meaningful.

Response rates by disease phase were examined relative to an a priori value of 2.5% using a one-sided lower 95% exact binomial confidence limit. If the lower limit from the one-sided lower 95% confidence limit exceeds 2.5%, the observed response rate will have exceeded the minimum threshold required to demonstrate efficacy.

Time Frame Day 1 up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 62 20 21 103
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
77.4 [1] 
(65.03 to NA)
55.0 [1] 
(31.53 to NA)
9.5 [1] 
(1.17 to NA)
59.2 [1] 
(49.10 to NA)
[1]
Lower limit of the 2-sided 95% CI is reported
2.Primary Outcome
Title Percentage of Participants Achieving a Major Cytogenetic Response by Subpopulation and Total Population
Hide Description

Subpopulations reflect chronic myeloid leukemia (CML) phases at the time of enrollment: chronic, accelerated, and blast phase. Primary endpoints as adjudicated by the Data Monitoring Committee were used for the primary analyses.

Major cytogenetic response includes complete or partial response. Both confirmed and unconfirmed major cytogenetic response is considered meaningful.

Unconfirmed response is based on a single bone marrow cytogenetic evaluation for participants where a confirmatory evaluation is not available.

Complete response shows 0% Philadelphia chromosome positive (Ph+) cells. A partial response shows >0% - 35% Ph+ cells.

Response rates by disease phase were examined relative to an a priori value of 2.5% using a one-sided lower 95% exact binomial confidence limit. If the lower limit from the one-sided lower 95% confidence limit exceeds 2.5%, the observed response rate will have exceeded the minimum threshold required to demonstrate efficacy.

Time Frame Day 1 up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 62 20 21 103
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
22.6 [1] 
(12.93 to NA)
5.0 [1] 
(0.13 to NA)
0
(0 to 0)
14.6 [1] 
(8.39 to NA)
[1]
Lower limit of the 2-sided 95% CI is reported
3.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Subpopulation and Total
Hide Description

TEAE are any untoward events that were newly occurring or worsening from Baseline.

Treatment related toxicity was considered by the investigator to be unrelated, possibly, probably or unknown related to study drug.

Severity was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death.

A serious adverse event (SAE) is any untoward medical occurrence that is fatal or life-threatening; results in persistent or significant disability or incapacity; requires or prolongs in-patient hospitalization; is a congenital anomaly/birth defect in the offspring of a patient; and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

A participant is only counted once in each category (at worst severity or strongest relationship).

Time Frame up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 62 20 21 103
Measure Type: Number
Unit of Measure: participants
>=1 TEAE 61 20 21 102
>= 1 SAE 36 12 19 67
Worst severity: Grade 1 0 1 0 1
Worst severity: Grade 2 6 2 1 9
Worst severity: Grade 3 9 4 4 17
Worst severity: Grade 4 37 9 4 50
Worst severity: Grade 5 9 4 12 25
Relation to drug: Unrelated 1 3 3 7
Relation to drug: Possibly 6 3 5 14
Relation to drug: Probably 54 13 13 80
Relation to drug: Unknown 0 1 0 1
With hematologic toxicity 55 13 13 81
Discontinued treatment due to AE 18 10 11 39
Deaths during study or follow-up 31 14 19 64
Deaths during study (outcome of SAE) 9 4 12 25
4.Secondary Outcome
Title Percentage of Participants in Each Cytogenetic Response Category Representing the Degree of Suppression of the Philadelphia Chromosome (Ph+)
Hide Description

Cytogenetic response categories:

  • Complete: 0% Ph+ cells
  • Partial: >0%-35% Ph+ cells
  • Minor: >35%-65% Ph+ cells
  • Minimal: >65%-95% Ph+ cells
  • No Response: >95% Ph+ cells
  • Unevaluable: <20 metaphases were examined and/or response could not be assigned
Time Frame Day 1 up to Month 9
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 62 20 21 103
Measure Type: Number
Unit of Measure: percentage of participants
Complete 16.1 5.0 0 10.7
Partial 6.5 0 0 3.9
Minor 4.8 0 0 2.9
Minimal 16.1 5.0 9.5 12.6
No Response 37.1 30.0 38.1 35.9
Unevaluable 19.4 60.0 52.4 34.0
5.Secondary Outcome
Title Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene GUS
Hide Description MMR is defined as a ratio of BCR-ABL/standard gene of less than 0.1% according to the international scale. BCR-ABL is a fusion gene of the breakpoint cluster region [BCR] gene and Abelson proto-oncogene [ABL] genes). This analysis used the standard gene GUS. Analysis was performed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) of peripheral blood.
Time Frame Day 1 up to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population of participants who had evaluable samples. Participants with no data for these analyses either had degraded samples or the samples were missing.
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 37 8 4 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
8.1
(1.7 to 21.9)
12.5
(0.3 to 52.7)
0 [1] 
(NA to NA)
8.2
(2.3 to 19.6)
[1]
no participants met criteria
6.Secondary Outcome
Title Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene ABL
Hide Description MMR is defined as a ratio of BCR-ABL/standard gene of less than 0.1% according to the international scale. BCR-ABL is a fusion gene of the breakpoint cluster region [BCR] gene and Abelson proto-oncogene [ABL] genes). This analysis used the standard gene ABL. Analysis was performed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) of peripheral blood.
Time Frame Day 1 up to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population of participants who had evaluable samples. Participants with no data for these analyses either had degraded samples or the samples were missing.
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 52 13 8 73
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
19.2
(9.6 to 32.5)
15.4
(1.9 to 45.5)
0 [1] 
(NA to NA)
16.4
(8.8 to 27.0)
[1]
no participants met criteria
7.Secondary Outcome
Title Percentage of Participants in Each Hematologic Response Category
Hide Description

Complete Response (CHR)

  • Chronic phase must last at least 8 weeks: WBC <10*10^9/liter, platelets <450*10^9/liter, myelocytes + metamyelocytes <5% in blood, no blasts or promyelocytes in blood, <20% basophils in peripheral blood, no extramedullary involvement.
  • Accelerated and Blast phase must last at least 4 weeks: absolute neutrophil count 1.5*10^9/liter, platelets 100*10^9/liter, no blood blasts, bone marrow blasts <5%, no extramedullary disease.

Partial Response - CHR plus one or more of the following:

  • Persistence of splenomegaly with a reduction of ≥50% from pre-treatment
  • Platelets > 450*10^9/L
  • Presence of immature cells in the peripheral blood
  • 5% to 25% blasts in the bone marrow
  • If extra-medullary disease pre-treatment, reduction by ≥50% Hematologic Improvement - CHR, except allowing persistent thrombocytopenia (<100*10^9/L), and a few immature cells No evidence of leukemia: Morphologic leukemia-free state, defined as <5% bone marrow blasts.
Time Frame Day 1 up to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 62 20 21 103
Measure Type: Number
Unit of Measure: percentage of participants
Complete response 77.4 45.0 4.8 56.3
Partial response 0 0 0 0
Hematologic improvement 0 0 4.8 1.0
Return to chronic phase NA [1]  5.0 4.8 1.9
No evidence of leukemia NA [2]  5.0 0 1.0
No response 19.4 25.0 81.0 33.0
Unevaluable 3.2 20.0 4.8 6.8
[1]
Participants enrolled in chronic phase and therefore cannot respond (improve) to chronic phase.
[2]
An overall hematologic response for chronic phase participants only included a complete hematologic response.
8.Secondary Outcome
Title Percentage of Participants With Extramedullary Disease (EMD) at Baseline Achieving a Clinical Response
Hide Description

Clinical response was defined by disease phase and based on evaluations by the independent Data Monitoring Committee (DMC).

Chronic Phase subgroup: achieving a complete hematologic response and/or major cytogenetic response (complete cytogenetic response or partial cytogenetic response, confirmed or unconfirmed).

Accelerated Phase and Blast Phase subgroups: achieving complete hematologic response, no evidence of leukemia, return to chronic phase, and/or major cytogenetic response (complete cytogenetic response or partial cytogenetic response, confirmed or unconfirmed).

The percentage of participants achieving response with extramedullary disease at Baseline was to be summarized, if the sample size was sufficient. This analysis was not done as the sample was ultimately insufficient

Time Frame Day 1 up to Month 9
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Hide Analysis Population Description
Intent to treat population of study participants who had extramedullary disease at baseline. Analysis not performed due to insufficient sample size.
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Percentage of Participants With the Largest Percentage Reduction From Baseline of T315I Mutated BCR-ABL
Hide Description Summarization is based on the best of the individual response assessments. Not assessable indicates that the participant either had no baseline assessment or the % mutation could not be determined in the post-baseline assessment(s).
Time Frame Day 1 up to Month 9
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population of participants with post-baseline assessment of T315I mutated BCR ABL
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 50 13 8 71
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
100% reduction
6.0
(2.0 to 25.0)
0
(0 to 0)
0
(0 to 0)
4.2
(1.3 to 17.5)
75-99% reduction
4.0
(0.8 to 20.8)
0
(0 to 0)
25.0
(4.3 to 77.7)
5.6
(2.4 to 20.4)
50-74% reduction
14.0
(9.3 to 40.0)
0
(0 to 0)
12.5
(0.4 to 64.1)
11.3
(7.7 to 30.8)
25-49% reduction
18.0
(13.8 to 46.8)
15.4
(2.8 to 60.0)
0
(0 to 0)
15.5
(12.3 to 38.0)
1-24% reduction
8.0
(3.5 to 29.0)
38.5
(21.2 to 86.3)
12.5
(0.4 to 64.1)
14.1
(10.7 to 35.7)
0% reduction
14.0
(9.3 to 40.0)
15.4
(2.8 to 60.0)
25.0
(4.3 to 77.7)
15.5
(12.3 to 38.0)
Not assessable
36.0 [1] 
(NA to NA)
30.8 [1] 
(NA to NA)
25.0 [1] 
(NA to NA)
33.8 [1] 
(NA to NA)
[1]
95% CI not calculated for a non-response category.
10.Secondary Outcome
Title Number of Treatment Cycles Needed to Achieve Best Hematologic Response
Hide Description Induction therapy was administered for 14 consecutive days for each 28 days cycle, for up to 6 cycles. All treatment arms were given omacetaxine mepesuccinate via subcutaneous (SC) administration at 1.25 mg/m^2 twice a day (BID) for the 14 consecutive days.
Time Frame Day 1 up to Month 6
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Hide Analysis Population Description
Intent to treat population of participants who had a response to treatment
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 48 11 2 61
Median (Full Range)
Unit of Measure: treatment cycles
1.0
(1 to 5)
1.0
(1 to 3)
1.0
(1 to 1)
1.0
(1 to 5)
11.Secondary Outcome
Title Number of Treatment Cycles Needed to Achieve Best Cytogenetic Response
Hide Description [Not Specified]
Time Frame Day 1 up to 22 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population of participants who had a cytogenetic response
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 27 2 2 31
Median (Full Range)
Unit of Measure: treatment cycles
3.0
(1 to 22)
2.5
(2 to 3)
2.0
(1 to 3)
3.0
(1 to 22)
12.Secondary Outcome
Title Kaplan-Meier Estimates for Time to Onset of Best Hematologic Response
Hide Description

Time to onset was analyzed using Kaplan-Meier estimates. Participants who did not achieve a response are censored at their last visit day.

Overall hematologic response for chronic phase participants includes confirmed complete hematologic response (CHR). Overall hematologic response for accelerated or blast phase participants includes confirmed complete hematologic response (CHR), no evidence of leukemia (NEL), or return to chronic phase (RCP). Hematologic response must last >= 8 weeks to be considered meaningful.

Time Frame Day 1 up to Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 62 20 21
Median (95% Confidence Interval)
Unit of Measure: months
0.46
(0.39 to 0.92)
1.74 [1] 
(0.00 to NA)
NA [1] 
(NA to NA)
[1]
A large percentage of participants were censored.
13.Secondary Outcome
Title Kaplan-Meier Estimates for Time to Onset of Best Cytogenetic Response
Hide Description

Time to onset was analyzed using Kaplan-Meier estimates. Participants who did not achieve a response are censored at their last visit day.

Major cytogenetic response includes complete or partial response. Both confirmed and unconfirmed major cytogenetic response is considered meaningful.

Unconfirmed response is based on a single bone marrow cytogenetic evaluation for participants where a confirmatory evaluation is not available.

Complete response shows 0% Philadelphia chromosome positive (Ph+) cells. A partial response shows >0% - 35% Ph+ cells.

Time Frame up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 62 20 21
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
A large percentage of participants were censored.
14.Secondary Outcome
Title Kaplan-Meier Estimates for Duration of Best Hematologic Response
Hide Description Duration of response is defined as the time from first reported date of hematologic response until the earliest date of objective evidence of disease progression, relapse or death. Data was censored at the last examination date for participants with ongoing response or participants who discontinued treatment for reasons other than adverse event, disease progression or death.
Time Frame up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population of participants who had a response
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 48 11 2
Median (Full Range)
Unit of Measure: months
9.08
(1.61 to 71.38)
3.59
(1.25 to 25.46)
3.31
(1.68 to 4.93)
15.Secondary Outcome
Title Kaplan-Meier Estimates for Duration of Best Cytogenetic Response
Hide Description Duration of response is defined as the time from first reported date of cytogenetic response until the earliest date of objective evidence of disease progression, relapse or death. Data was censored at the last examination date for participants with ongoing response or participants who discontinued treatment for reasons other than adverse event, disease progression or death.
Time Frame up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population of participants who had a response
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 14 1 0
Median (Full Range)
Unit of Measure: months
6.64
(2.34 to 59.38)
16.35
(16.35 to 16.35)
16.Secondary Outcome
Title Kaplan-Meier Estimates for Time to Disease Progression
Hide Description Time to disease progression is defined as the time from the initiation of treatment until the onset date of death, the development of CML accelerated phase or blast phase, or the loss of complete hematologic response or major cytogenetic response, whichever came first. Participants were censored only if they did not have progression or if they discontinued treatment for reasons other than AE, progression or death.
Time Frame up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 62 20 21 103
Median (95% Confidence Interval)
Unit of Measure: months
7.73
(5.79 to 11.02)
4.74
(1.81 to 9.01)
2.20
(1.48 to 3.26)
5.86
(3.88 to 7.04)
17.Secondary Outcome
Title Kaplan-Meier Estimates for Overall Survival
Hide Description Overall survival is defined as the time from the initiation of treatment until death from any cause or the last day of participant contact or evaluation for participants that were lost to follow-up. Participants were censored t the last recorded contract or evaluation when a participant was alive at time of analysis. A quarterly phone survey was conducted to collect survival data for participants who discontinued from the study.
Time Frame up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat
Arm/Group Title CML: Chronic Phase CML: Accelerated Phase CML: Blast Phase Total Participants
Hide Arm/Group Description:
Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Treatment included induction therapy of subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years.
Overall Number of Participants Analyzed 62 20 21 103
Median (95% Confidence Interval)
Unit of Measure: months
49.31 [1] 
(24.97 to NA)
18.72
(4.74 to 32.07)
3.45
(2.20 to 4.84)
21.51
(12.01 to 36.88)
[1]
A large percentage of participants were censored
Time Frame up to 4 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Omacetaxine
Hide Arm/Group Description Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 24 months.
All-Cause Mortality
Omacetaxine
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Omacetaxine
Affected / at Risk (%) # Events
Total   67/103 (65.05%)    
Blood and lymphatic system disorders   
Anaemia * 1  5/103 (4.85%)  5
Bone marrow failure * 1  8/103 (7.77%)  10
Bone marrow necrosis * 1  1/103 (0.97%)  1
Febrile bone marrow aplasia * 1  2/103 (1.94%)  2
Febrile neutropenia * 1  12/103 (11.65%)  14
Haematotoxicity * 1  1/103 (0.97%)  1
Leukocytosis * 1  1/103 (0.97%)  1
Leukopenia * 1  1/103 (0.97%)  1
Leukostasis * 1  1/103 (0.97%)  1
Neutropenia * 1  3/103 (2.91%)  4
Pancytopenia * 1  6/103 (5.83%)  6
Thrombocytopenia * 1  12/103 (11.65%)  17
Cardiac disorders   
Acute coronary syndrome * 1  1/103 (0.97%)  1
Arrhythmia * 1  2/103 (1.94%)  2
Coronary artery disease * 1  1/103 (0.97%)  1
Extrasystoles * 1  1/103 (0.97%)  1
Left ventricular failure * 1  1/103 (0.97%)  1
Congenital, familial and genetic disorders   
Chromosomal deletion * 1  1/103 (0.97%)  1
Endocrine disorders   
Diabetes insipidus * 1  1/103 (0.97%)  1
Gastrointestinal disorders   
Anal fissure * 1  1/103 (0.97%)  1
Gastrointestinal haemorrhage * 1  2/103 (1.94%)  2
General disorders   
Aplasia * 1  1/103 (0.97%)  1
Chest pain * 1  1/103 (0.97%)  1
Death * 1  1/103 (0.97%)  1
Disease progression * 1  12/103 (11.65%)  12
General physical health deterioration * 1  1/103 (0.97%)  1
Pyrexia * 1  2/103 (1.94%)  2
Hepatobiliary disorders   
Cholecystitis * 1  1/103 (0.97%)  1
Infections and infestations   
Abscess limb * 1  1/103 (0.97%)  1
Bronchopulmonary aspergillosis * 1  1/103 (0.97%)  1
Cellulitis * 1  2/103 (1.94%)  2
Gastroenteritis * 1  1/103 (0.97%)  1
Gastroenteritis viral * 1  1/103 (0.97%)  1
Influenza * 1  1/103 (0.97%)  1
Pneumonia * 1  2/103 (1.94%)  2
Sepsis * 1  3/103 (2.91%)  3
Staphylococcal bacteraemia * 1  1/103 (0.97%)  1
Subcutaneous abscess * 1  2/103 (1.94%)  2
Injury, poisoning and procedural complications   
Subdural haematoma * 1  1/103 (0.97%)  1
Transfusion reaction * 1  2/103 (1.94%)  2
Metabolism and nutrition disorders   
Hyperglycaemic hyperosmolar nonketotic syndrome * 1  1/103 (0.97%)  1
Musculoskeletal and connective tissue disorders   
Back pain * 1  1/103 (0.97%)  1
Bone pain * 1  3/103 (2.91%)  3
Musculoskeletal chest pain * 1  1/103 (0.97%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Blast cell crisis * 1  2/103 (1.94%)  2
Breast cancer * 1  1/103 (0.97%)  1
Chronic myeloid leukaemia * 1  2/103 (1.94%)  2
Leukaemic infiltration extramedullary * 1  1/103 (0.97%)  1
Myelodysplastic syndrome * 1  1/103 (0.97%)  1
Myelofibrosis * 1  1/103 (0.97%)  1
Tumour lysis syndrome * 1  1/103 (0.97%)  1
Nervous system disorders   
Carotid artery stenosis * 1  1/103 (0.97%)  1
Cerebral haemorrhage * 1  2/103 (1.94%)  2
Convulsion * 1  1/103 (0.97%)  1
Transient ischaemic attack * 1  2/103 (1.94%)  2
Psychiatric disorders   
Confusional state * 1  1/103 (0.97%)  1
Delirium * 1  1/103 (0.97%)  1
Mental status changes * 1  1/103 (0.97%)  1
Renal and urinary disorders   
Renal failure chronic * 1  1/103 (0.97%)  1
Respiratory, thoracic and mediastinal disorders   
Acute respiratory distress syndrome * 1  1/103 (0.97%)  1
Chronic obstructive pulmonary disease * 1  1/103 (0.97%)  1
Epistaxis * 1  1/103 (0.97%)  1
Pulmonary haemorrhage * 1  1/103 (0.97%)  1
Skin and subcutaneous tissue disorders   
Pyoderma gangrenosum * 1  1/103 (0.97%)  1
Vascular disorders   
Deep vein thrombosis * 1  1/103 (0.97%)  1
Orthostatic hypotension * 1  1/103 (0.97%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Omacetaxine
Affected / at Risk (%) # Events
Total   100/103 (97.09%)    
Blood and lymphatic system disorders   
Anaemia * 1  56/103 (54.37%)  196
Bone marrow failure * 1  8/103 (7.77%)  10
Febrile neutropenia * 1  15/103 (14.56%)  21
Leukocytosis * 1  10/103 (9.71%)  20
Leukopenia * 1  18/103 (17.48%)  64
Lymphopenia * 1  13/103 (12.62%)  39
Neutropenia * 1  48/103 (46.60%)  139
Pancytopenia * 1  15/103 (14.56%)  22
Thrombocytopenia * 1  67/103 (65.05%)  253
Cardiac disorders   
Tachycardia * 1  8/103 (7.77%)  8
Gastrointestinal disorders   
Abdominal pain * 1  14/103 (13.59%)  26
Abdominal pain upper * 1  14/103 (13.59%)  16
Constipation * 1  18/103 (17.48%)  18
Diarrhoea * 1  40/103 (38.83%)  107
Dry mouth * 1  6/103 (5.83%)  6
Gingival bleeding * 1  8/103 (7.77%)  9
Mouth ulceration * 1  8/103 (7.77%)  8
Nausea * 1  36/103 (34.95%)  96
Vomiting * 1  15/103 (14.56%)  17
General disorders   
Asthenia * 1  22/103 (21.36%)  59
Chest pain * 1  7/103 (6.80%)  10
Chills * 1  7/103 (6.80%)  7
Disease progression * 1  18/103 (17.48%)  19
Fatigue * 1  35/103 (33.98%)  65
Injection site bruising * 1  8/103 (7.77%)  8
Injection site erythema * 1  17/103 (16.50%)  66
Injection site pain * 1  8/103 (7.77%)  10
Injection site reaction * 1  7/103 (6.80%)  7
Mucosal inflammation * 1  6/103 (5.83%)  8
Oedema peripheral * 1  20/103 (19.42%)  30
Pyrexia * 1  30/103 (29.13%)  36
Hepatobiliary disorders   
Hyperbilirubinaemia * 1  7/103 (6.80%)  17
Infections and infestations   
Oral herpes * 1  7/103 (6.80%)  8
Pneumonia * 1  6/103 (5.83%)  6
Upper respiratory tract infection * 1  11/103 (10.68%)  15
Injury, poisoning and procedural complications   
Contusion * 1  6/103 (5.83%)  6
Metabolism and nutrition disorders   
Anorexia * 1  12/103 (11.65%)  12
Decreased appetite * 1  6/103 (5.83%)  6
Hyperglycaemia * 1  6/103 (5.83%)  8
Hyperuricaemia * 1  10/103 (9.71%)  20
Hypokalaemia * 1  6/103 (5.83%)  7
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  22/103 (21.36%)  39
Back pain * 1  10/103 (9.71%)  13
Bone pain * 1  12/103 (11.65%)  17
Myalgia * 1  10/103 (9.71%)  12
Pain in extremity * 1  12/103 (11.65%)  19
Nervous system disorders   
Dizziness * 1  8/103 (7.77%)  9
Headache * 1  15/103 (14.56%)  26
Psychiatric disorders   
Anxiety * 1  6/103 (5.83%)  6
Insomnia * 1  14/103 (13.59%)  16
Respiratory, thoracic and mediastinal disorders   
Cough * 1  20/103 (19.42%)  24
Dyspnoea * 1  11/103 (10.68%)  15
Epistaxis * 1  19/103 (18.45%)  25
Skin and subcutaneous tissue disorders   
Alopecia * 1  14/103 (13.59%)  14
Dry skin * 1  8/103 (7.77%)  10
Erythema * 1  6/103 (5.83%)  8
Night sweats * 1  6/103 (5.83%)  9
Petechiae * 1  7/103 (6.80%)  8
Pruritus * 1  8/103 (7.77%)  10
Rash * 1  15/103 (14.56%)  20
Vascular disorders   
Haematoma * 1  7/103 (6.80%)  7
Hypertension * 1  8/103 (7.77%)  9
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc.
Phone: 215-591-3000
EMail: ustevatrials@tevapharm.com
Layout table for additonal information
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products R&D, Inc. )
ClinicalTrials.gov Identifier: NCT00375219    
Other Study ID Numbers: CGX-635-CML-202
2006-000176-32 ( EudraCT Number )
First Submitted: September 8, 2006
First Posted: September 12, 2006
Results First Submitted: May 5, 2014
Results First Posted: June 3, 2014
Last Update Posted: June 3, 2014