A Study of Clofarabine in Combination With Etoposide and Cyclophosphamide in Children With Acute Leukemias. - Study Results

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Acute Lymphoblastic Leukemia Acute Myelogenous Leukemia Relapsed Leukemia
Interventions:	Drug: clofarabine Drug: Etoposide Drug: Cyclophosphamide

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Clofarabine, Etoposide, Cyclophosphamide	Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m^2, etoposide dosage from 75-100 mg/m^2, cyclophosphamide dosage from 340-440 mg/m^2. > Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously

Participant Flow for 2 periods

Period 1: Phase 1

	Clofarabine, Etoposide, Cyclophosphamide
STARTED	25
COMPLETED	0 ^[1]
NOT COMPLETED	25
Refused further treatment	1
Failure to achieve response	8
Disease relapse	4
Scheduled for transplant	9
Death	3

[1]	No Phase 1 participants completed the treatment period (i.e. all 8 cycles and follow-up)

Period 2: Phase 2

	Clofarabine, Etoposide, Cyclophosphamide
STARTED	25 ^[1]
COMPLETED	0 ^[2]
NOT COMPLETED	25
Physician Decision	4
Adverse Event	1
Failure to achieve response	3
Disease relapse	1
Scheduled for transplant	8
Unspecified	1
Death	7

[1]	Phase 1 and phase 2 are separate populations
[2]	No Phase 2 participants completed the treatment period (i.e. all 8 cycles and follow-up)

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Phase 1: Clofarabine, Etoposide, Cyclophosphamide	Phase 1: escalating dosage of the three drugs delivered intravenously. Clofarabine dosage from 20-40 mg/m^2, etoposide dosage from 75-100 mg/m^2, cyclophosphamide dosage from 340-440 mg/m^2.
Phase 2: Clofarabine, Etoposide, Cyclophosphamide	Phase 2: The recommended phase 2 doses (RP2D) were clofarabine 40 mg/m^2, etoposide 100 mg/m^2 and cyclophosphamide 440 mg/m^2 delivered intravenously

Baseline Measures

	Phase 1: Clofarabine, Etoposide, Cyclophosphamide	Phase 2: Clofarabine, Etoposide, Cyclophosphamide	Total
Number of Participants [units: participants]	25	25	50
Age ^[1] [units: years] Mean ± Standard Deviation	9.1 ± 5.03	13.2 ± 5.25	11.2 ± 5.49
Gender ^[1] [units: participants]
Female	10	9	19
Male	15	16	31
Ethnicity (NIH/OMB) ^[1] [units: participants]
Hispanic or Latino	5	10	15
Not Hispanic or Latino	20	15	35
Unknown or Not Reported	0	0	0
Race (NIH/OMB) ^[1] [units: participants]
American Indian or Alaska Native	0	1	1
Asian	3	2	5
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	4	2	6
White	16	12	28
More than one race	0	0	0
Unknown or Not Reported	2	8	10
Percent Leukemic Blast Cells ^[2] [units: percentage of total blast cells] Mean ± Standard Deviation	66.8 ± 24.85	69.52 ± 23.566	68.16 ± 24.008
Absolute Neutrophil Counts ^[1] [units: 10^9/L] Mean ± Standard Deviation	1.93828 ± 3.049992	1.9280 ± 1.708126	1.93325 ± 2.459536
White Blood Cell Counts ^[1] [units: 10^9/L] Mean ± Standard Deviation	8.323 ± 9.1305	12.171 ± 23.0150	10.247 ± 17.4370
Immunophenotype ^[3] [units: participants]
B cell	13	21	34
T cell	5	1	6
Unknown	2	3	5
not included (AML participants)	5	0	5
Count of Previous Anti-Leukemic (non-transplant) Treatment Regimens ^[1] [units: participants]
1 regimen	4	4	8
2 regimens	18	14	32
3 regimens	3	7	10
Participants with Previous Anti-Leukemic Transplant Regimens ^[1] [units: participants]
Transplants	4	4	8
No transplants	21	21	42
Participants Who Were Refractory to the Most Recent Previous Anti-Leukemic Treatment ^[4] [units: participants]
Yes	7	15	22
No	18	10	28
Participant Rating Using the Karnofsky/Lansky Performance Status Scale ^[5] [units: participants]
50	0	2	2
60	0	2	2
70	1	2	3
80	5	3	8
90	7	6	13
100	12	10	22

[1]	The two study phases were not designed to be reported in the aggregate.
[2]	Percent of leukemic blast cells based on bone marrow aspirate. The two study phases were not designed to be reported in the aggregate.
[3]	Applies to acute lymphoblastic leukemic (ALL) participants only. Acute myelogenous leukemic (AML) participants are not included. The two study phases were not designed to be reported in the aggregate.
[4]	The answer "Yes" indicates the number of participants who were refractory (unresponsive) to the most recent anti-leukemic treatment. The answer "No" represents participants who were not refractory. The two study phases were not designed to be reported in the aggregate.
[5]	Baseline performance was rating using either the Karnofsky Performance Scale for participants greater than 10 years old, or the Lansky Performance Scale for participants 10 years or younger. Both scales range from 0-100 with 0 indicating dead or unresponsive and 100 indicating normal performance. The two study phases were not designed to be reported in the aggregate.

Outcome Measures

Show All Outcome Measures

1. Primary:

Maximum Tolerated Dose (MTD) in Phase 1 [ Time Frame: Up to Day 42 (Phase 1 portion of study) ]

Show Outcome Measure 1

2. Primary:

Participants With Dose Limiting Toxicity in Phase 1 [ Time Frame: Up to Day 42 (Phase 1 portion of study) ]

Show Outcome Measure 2

3. Primary:

Percentage of Participants Achieving A Response Over the First Two Treatment Cycles in Phase 2 [ Time Frame: Approximately 28-56 days (Phase 2 portion of study) ]

Show Outcome Measure 3

4. Secondary:

Summary of Participants With Adverse Events (AEs) in Phase 1 [ Time Frame: Up to 9.5 months (Phase 1 portion of study) ]

Show Outcome Measure 4

5. Secondary:

Percentage of Participants Achieving A Response Over the First Two Treatment Cycles in Phase 1 [ Time Frame: Approximately 2 months (Phase 1 portion of study) ]

Show Outcome Measure 5

6. Secondary:

Time to Remission for Participants Who Had a Response in Phase 1 [ Time Frame: up to 8 weeks (Phase 1 portion of study) ]

Show Outcome Measure 6

7. Secondary:

Kaplan Meier Estimate of Duration of Remission (DOR) for Participants Who Achieved Overall Remission (OR) in Phase 1 [ Time Frame: Up to 2 years (Phase 1 portion of study) ]

Show Outcome Measure 7

8. Secondary:

Kaplan Meier Estimates of Event-free Survival (EFS) for Participants in Phase 1 [ Time Frame: Up to 2 years (Phase 1 portion of study) ]

Show Outcome Measure 8

9. Secondary:

Number of Participants With 4-month Event Free Survival in Phase 1 [ Time Frame: 4 months (Phase I portion of study) ]

Show Outcome Measure 9

10. Secondary:

Kaplan Meier Estimates of Overall Survival (OS) for Participants in Phase 1 [ Time Frame: Up to 2 years (Phase 1 portion of study) ]

Show Outcome Measure 10

11. Secondary:

Summary of Participants With Adverse Events (AEs) in Phase 2 [ Time Frame: Up to 9.5 months (Phase 2 portion of study) ]

Show Outcome Measure 11

12. Secondary:

Time to Remission for Participants Who Had a Response in Phase 2 [ Time Frame: up to 8 weeks (Phase 2 portion of study) ]

Show Outcome Measure 12

13. Secondary:

Kaplan Meier Estimate of Duration of Remission (DOR) for Participants Who Achieved Overall Remission (OR) in Phase 2 [ Time Frame: Up to 2 years (Phase 2 portion of study) ]

Show Outcome Measure 13

14. Secondary:

Kaplan Meier Estimates of Event-free Survival (EFS) for Participants in Phase 2 [ Time Frame: Up to 2 years (Phase 2 portion of study) ]

Show Outcome Measure 14

15. Secondary:

Number of Participants With 4-month Event Free Survival in Phase 2 [ Time Frame: 4 months (Phase 2 portion of study) ]

Show Outcome Measure 15

16. Secondary:

Kaplan Meier Estimates of Overall Survival (OS) for Participants in Phase 2 [ Time Frame: Up to 2 years (Phase 2 portion of study) ]

Show Outcome Measure 16

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: In multi-site studies, PI can publish after Genzyme publishes or 18 months after study completion. PI gives Genzyme a draft 60 days before publication. Genzyme can ask that confidential information be removed, and can defer publication another 60 days upon notifying PI that it will file a patent application on inventions contained in the draft.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Genzyme Medical Information
Organization: Genzyme Corporation
phone: 1-800-745-4447

No publications provided by Genzyme

Publications automatically indexed to this study:

Hijiya N, Thomson B, Isakoff MS, Silverman LB, Steinherz PG, Borowitz MJ, Kadota R, Cooper T, Shen V, Dahl G, Thottassery JV, Jeha S, Maloney K, Paul JA, Barry E, Carroll WL, Gaynon PS. Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. Blood. 2011 Dec 1;118(23):6043-9. Epub 2011 Oct 3.

Responsible Party:	Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier:	NCT00315705 History of Changes
Other Study ID Numbers:	CLO21800205
Study First Received:	April 18, 2006
Results First Received:	April 27, 2011
Last Updated:	June 10, 2011
Health Authority:	United States: Food and Drug Administration