Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 12 of 16 for:    LENALIDOMIDE AND Leukemia AND Azacitidine

Lenalidomide and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndromes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00352001
Recruitment Status : Completed
First Posted : July 14, 2006
Results First Posted : September 19, 2018
Last Update Posted : September 19, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mikkael Sekeres MD, Case Comprehensive Cancer Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Leukemia
Myelodysplastic Syndromes
Interventions Drug: azacitidine
Drug: lenalidomide
Enrollment 37
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Lenalidomide and Azacitidine
Hide Arm/Group Description

azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Period Title: Overall Study
Started 37
Azacitidine 75mg/Lenalidomide 5mg-14 Day 3
Azacitidine 75mg/Lenalidomide 5mg-21 Day 3
Azacitidine 75mg/Lenalidomide 10mg-14day 3
Completed 37
Not Completed 0
Arm/Group Title Lenalidomide and Azacitidine
Hide Arm/Group Description

azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Overall Number of Baseline Participants 37
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 37 participants
76.5
(54 to 88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Female
13
  35.1%
Male
24
  64.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Hispanic or Latino
2
   5.4%
Not Hispanic or Latino
28
  75.7%
Unknown or Not Reported
7
  18.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   2.7%
White
36
  97.3%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 37 participants
37
1.Primary Outcome
Title PHASE I: Maximum Tolerated Dose of Azacitidine
Hide Description Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard “3+3” design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.
Time Frame After 1 courses (1 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Phase I
Arm/Group Title Lenalidomide and Azacitidine
Hide Arm/Group Description:

azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: mg/m2 subcutaneously for 5 days
75
2.Primary Outcome
Title PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
Hide Description

For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement.

Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones.

Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality.

Hematologic Improvement (HI) is defined as: red blood cell increase of >=1.5g/dL, a platelet response of >=30X10^9/L or by at least 100% for values starting <20X10^9/L, or a neutrophil response of at least 100% and absolute increase of >0.5X10^9/L

Time Frame After 4 courses (4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat
Arm/Group Title Lenalidomide and Azacitidine
Hide Arm/Group Description:

azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: participants
26
3.Primary Outcome
Title PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
Hide Description

For the Phase II study portion, to determine the efficacy (measured as response rate) of the combination therapy as defined by the International Working Group (IWG) criteria (CR, complete remission; PR, partial remission; or HI, hematological improvement)

Complete response (CR) is defined as: Disappearance of the chromosomal abnormality without appearance of new ones.

Partial response (PR) is defined as: At least 50% reduction of the chromosomal abnormality.

Hematologic Improvement (HI) is defined as: red blood cell increase of >=1.5g/dL, a platelet response of >=30X10^9/L or by at least 100% for values starting <20X10^9/L, or a neutrophil response of at least 100% and absolute increase of >0.5X10^9/L

Time Frame After 7 courses (months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat
Arm/Group Title Lenalidomide and Azacitidine
Hide Arm/Group Description:

azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: participants
26
4.Primary Outcome
Title PHASE I: Maximum Tolerated Dose of Lenalidomide
Hide Description Participants will be enrolled on the Phase I study portion in blocks of 3 to varying doses of Revlimid® (lenalidomide) and Vidaza® (azacitidine) (Table 1). To determine the MTD, a standard “3+3” design will be used. DLT will be assessed during the first cycle of therapy within each treatment group. No Maximum dose was reach but the go-forward dose agreed upon by the investigators is reported here.
Time Frame After 1 courses (1 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Phase I
Arm/Group Title Lenalidomide and Azacitidine
Hide Arm/Group Description:

azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: mg orally for 21 days
10
5.Secondary Outcome
Title Time to Transformation to Acute Myeloid Leukemia or Death
Time Frame After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who achieved a complete response
Arm/Group Title Lenalidomide and Azacitidine
Hide Arm/Group Description:

azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Overall Number of Participants Analyzed 16
Median (Full Range)
Unit of Measure: months
13.6
(3 to 55)
6.Secondary Outcome
Title Time to Relapse After Achieving Complete Response
Hide Description [Not Specified]
Time Frame After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients with a complete response were analysed
Arm/Group Title Lenalidomide and Azacitidine
Hide Arm/Group Description:

azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Overall Number of Participants Analyzed 16
Median (Full Range)
Unit of Measure: months
17
(3 to 39)
7.Secondary Outcome
Title Number of Patients That Experience Grade 3 or 4 Treatment Related Non-hematologic Adverse Events
Hide Description [Not Specified]
Time Frame After 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intention to Treat
Arm/Group Title Lenalidomide and Azacitidine
Hide Arm/Group Description:

azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: participants
9
8.Secondary Outcome
Title Overall Survival Among Patients With Complete Response
Hide Description Time (in months) patients who achieved a complete response using the RECIST criteria were alive on study
Time Frame After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients with complete response
Arm/Group Title Lenalidomide and Azacitidine
Hide Arm/Group Description:

azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

Overall Number of Participants Analyzed 16
Median (Full Range)
Unit of Measure: months
37
(7 to 55)
Time Frame 28 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Lenalidomide and Azacitidine
Hide Arm/Group Description

azacitidine: Azacitidine subcutaneously once daily on days 1-5 or days 1-5 and 8-12. Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

lenalidomide: Oral lenalidomide once daily on days 1-14 or days 1-21.Treatment repeats every 28 days for up to 7 courses in the absence of relapse (after achieving complete or partial remission), disease progression, or unacceptable toxicity.

All-Cause Mortality
Lenalidomide and Azacitidine
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Lenalidomide and Azacitidine
Affected / at Risk (%) # Events
Total   10/37 (27.03%)    
Blood and lymphatic system disorders   
Febrile Neutropenia * 1  5/37 (13.51%)  6
Cardiac disorders   
Congestive Heart Failure * 1  1/37 (2.70%)  1
Myocardial Infarction * 1  1/37 (2.70%)  1
General disorders   
general disorder * 1  1/37 (2.70%)  1
Fatigue (lethargy, malaise, asthenia) * 1  1/37 (2.70%)  1
Constitutional Symptom * 1 [1]  1/37 (2.70%)  1
Infections and infestations   
Pneumonia * 1  1/37 (2.70%)  1
Infection * 1 [2]  1/37 (2.70%)  1
Investigations   
Hemoglobin for leukemia studies * 1  1/37 (2.70%)  1
Increased blood urea nitrogen (BUN) * 1  1/37 (2.70%)  1
Neutrophils/granulocytes * 1  2/37 (5.41%)  4
Platelets * 1  2/37 (5.41%)  4
Nervous system disorders   
CNS Hemorrhage/bleeding * 1  1/37 (2.70%)  1
weakness/dizziness * 1  1/37 (2.70%)  1
Renal and urinary disorders   
Acute kidney injury * 1  1/37 (2.70%)  1
Respiratory, thoracic and mediastinal disorders   
Pneumonitis/pulmonary infiltrates * 1  1/37 (2.70%)  1
Skin and subcutaneous tissue disorders   
Rash/desquamation * 1  2/37 (5.41%)  2
Vascular disorders   
Deep vein or cardiac thrombosis * 1  1/37 (2.70%)  1
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia * 1  1/37 (2.70%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (2.0)
[1]
Sudden death on study - unrelated to treatment
[2]
Catheter Related Infection
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Lenalidomide and Azacitidine
Affected / at Risk (%) # Events
Total   37/37 (100.00%)    
Blood and lymphatic system disorders   
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe * 1  11/37 (29.73%)  14
Hemoglobin * 1  16/37 (43.24%)  29
Cardiac disorders   
Cardiac Arrhythmia - Other * 1  3/37 (8.11%)  3
Cardiac General - Other * 1  3/37 (8.11%)  4
Gastrointestinal disorders   
Heartburn/dyspepsia * 1  4/37 (10.81%)  4
Vomiting * 1  4/37 (10.81%)  5
Gastrointestinal - Other * 1  5/37 (13.51%)  9
Nausea * 1  10/37 (27.03%)  11
Diarrhea * 1  18/37 (48.65%)  24
Constipation * 1  20/37 (54.05%)  22
General disorders   
Rigors/chills * 1  5/37 (13.51%)  5
Edema: limb * 1  5/37 (13.51%)  5
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) * 1  6/37 (16.22%)  6
Constitutional Symptoms - Other * 1  8/37 (21.62%)  23
Injection site reaction/extravasation changes * 1  17/37 (45.95%)  20
Pain * 1  19/37 (51.35%)  36
Fatigue (asthenia, lethargy, malaise) * 1  21/37 (56.76%)  24
Infections and infestations   
Infection with unknown ANC * 1  3/37 (8.11%)  3
Infection - Other * 1  6/37 (16.22%)  8
Investigations   
Weight loss * 1  4/37 (10.81%)  4
Leukocytes (total WBC) * 1  12/37 (32.43%)  34
Neutrophils/granulocytes (ANC/AGC) * 1  17/37 (45.95%)  29
Platelets * 1  18/37 (48.65%)  43
Metabolism and nutrition disorders   
Anorexia * 1  7/37 (18.92%)  7
Musculoskeletal and connective tissue disorders   
Musculoskeletal/Soft Tissue - Other * 1  3/37 (8.11%)  3
Nervous system disorders   
Taste alteration (dysgeusia) * 1  4/37 (10.81%)  5
Dizziness * 1  10/37 (27.03%)  10
Psychiatric disorders   
Neurology - Other * 1  5/37 (13.51%)  7
Insomnia * 1  6/37 (16.22%)  6
Respiratory, thoracic and mediastinal disorders   
Pulmonary/Upper Respiratory - Other * 1  6/37 (16.22%)  6
Cough * 1  8/37 (21.62%)  8
Dyspnea (shortness of breath) * 1  11/37 (29.73%)  11
Skin and subcutaneous tissue disorders   
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa) * 1  3/37 (8.11%)  4
Sweating (diaphoresis) * 1  4/37 (10.81%)  4
Dermatology/Skin - Other * 1  11/37 (29.73%)  19
Pruritus/itching * 1  12/37 (32.43%)  17
Rash/desquamation * 1  12/37 (32.43%)  19
Vascular disorders   
Hemorrhage/Bleeding - Other * 1  4/37 (10.81%)  7
Hypotension * 1  6/37 (16.22%)  8
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (2.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Mikkael Sekeres
Organization: CCCC
Phone: 216-445-9353
EMail: sekerem@ccf.org
Layout table for additonal information
Responsible Party: Mikkael Sekeres MD, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00352001     History of Changes
Obsolete Identifiers: NCT00326846
Other Study ID Numbers: CASE17Z05
P30CA016042 ( U.S. NIH Grant/Contract )
UCLA-0511032-01
UCLA-RDN-5405
UCLA-05011032-01
CASE17Z05 ( Other Identifier: Case Comprehensive Cancer Center )
First Submitted: July 13, 2006
First Posted: July 14, 2006
Results First Submitted: April 10, 2014
Results First Posted: September 19, 2018
Last Update Posted: September 19, 2018