Trial Outcomes & Findings for Lenalidomide and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndromes (NCT NCT00352001)
NCT ID: NCT00352001
Last Updated: 2018-09-19
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
37 participants
Primary outcome timeframe
After 1 courses (1 months)
Results posted on
2018-09-19
Participant Flow
Participant milestones
| Measure |
Lenalidomide and Azacitidine
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 Study
STARTED
|
37
|
|
Overall Study
Azacitidine 75mg/Lenalidomide 5mg-14 Day
|
3
|
|
Overall Study
Azacitidine 75mg/Lenalidomide 5mg-21 Day
|
3
|
|
Overall Study
Azacitidine 75mg/Lenalidomide 10mg-14day
|
3
|
|
Overall Study
COMPLETED
|
37
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Lenalidomide and Azacitidine in Treating Patients With Advanced Myelodysplastic Syndromes
Baseline characteristics by cohort
| Measure |
Lenalidomide and Azacitidine
n=37 Participants
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.
|
|---|---|
|
Age, Continuous
|
76.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
28 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
36 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
37 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After 1 courses (1 months)Population: Participants in Phase I
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.
Outcome measures
| Measure |
Lenalidomide and Azacitidine
n=18 Participants
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.
|
|---|---|
|
PHASE I: Maximum Tolerated Dose of Azacitidine
|
75 mg/m2 subcutaneously for 5 days
|
PRIMARY outcome
Timeframe: After 4 courses (4 months)Population: Intention to Treat
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
Outcome measures
| Measure |
Lenalidomide and Azacitidine
n=37 Participants
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.
|
|---|---|
|
PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
|
26 participants
|
PRIMARY outcome
Timeframe: After 7 courses (months)Population: Intention to Treat
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
Outcome measures
| Measure |
Lenalidomide and Azacitidine
n=37 Participants
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.
|
|---|---|
|
PHASE II: Determine the Number of Patients With Responses for Efficacy(Measured as Response Rate)
|
26 participants
|
PRIMARY outcome
Timeframe: After 1 courses (1 months)Population: Participants in Phase I
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.
Outcome measures
| Measure |
Lenalidomide and Azacitidine
n=18 Participants
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.
|
|---|---|
|
PHASE I: Maximum Tolerated Dose of Lenalidomide
|
10 mg orally for 21 days
|
SECONDARY outcome
Timeframe: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 monthsPopulation: Patients who achieved a complete response
Time (in months) patients took to evolve to myeloid leukemia or death after achieving a complete response using the RECIST criteria
Outcome measures
| Measure |
Lenalidomide and Azacitidine
n=16 Participants
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.
|
|---|---|
|
Time to Transformation to Acute Myeloid Leukemia or Death
|
13.6 months
Interval 3.0 to 55.0
|
SECONDARY outcome
Timeframe: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 monthsPopulation: Only patients with a complete response were analysed
Outcome measures
| Measure |
Lenalidomide and Azacitidine
n=16 Participants
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.
|
|---|---|
|
Time to Relapse After Achieving Complete Response
|
17 months
Interval 3.0 to 39.0
|
SECONDARY outcome
Timeframe: After 7 monthsPopulation: Intention to Treat
Outcome measures
| Measure |
Lenalidomide and Azacitidine
n=37 Participants
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.
|
|---|---|
|
Number of Patients That Experience Grade 3 or 4 Treatment Related Non-hematologic Adverse Events
|
9 participants
|
SECONDARY outcome
Timeframe: After 7 months of treatment, until the date of first documented myeloid leukemia or death, whichever came first, assessed up to 55 monthsPopulation: Only patients with complete response
Time (in months) patients who achieved a complete response using the RECIST criteria were alive on study
Outcome measures
| Measure |
Lenalidomide and Azacitidine
n=16 Participants
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 Survival Among Patients With Complete Response
|
37 months
Interval 7.0 to 55.0
|
Adverse Events
Lenalidomide and Azacitidine
Serious events: 10 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lenalidomide and Azacitidine
n=37 participants at risk
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.
|
|---|---|
|
Vascular disorders
Deep vein or cardiac thrombosis
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
General disorders
general disorder
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
Nervous system disorders
weakness/dizziness
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
General disorders
Fatigue (lethargy, malaise, asthenia)
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
Investigations
Hemoglobin for leukemia studies
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
Vascular disorders
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
Infections and infestations
Pneumonia
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
Investigations
Increased blood urea nitrogen (BUN)
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
Investigations
Neutrophils/granulocytes
|
5.4%
2/37 • Number of events 4 • 28 weeks
|
|
Investigations
Platelets
|
5.4%
2/37 • Number of events 4 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis/pulmonary infiltrates
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
5.4%
2/37 • Number of events 2 • 28 weeks
|
|
Renal and urinary disorders
Acute kidney injury
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
Infections and infestations
Infection
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
General disorders
Constitutional Symptom
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
13.5%
5/37 • Number of events 6 • 28 weeks
|
|
Cardiac disorders
Congestive Heart Failure
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
Cardiac disorders
Myocardial Infarction
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
|
Nervous system disorders
CNS Hemorrhage/bleeding
|
2.7%
1/37 • Number of events 1 • 28 weeks
|
Other adverse events
| Measure |
Lenalidomide and Azacitidine
n=37 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Cardiac Arrhythmia - Other
|
8.1%
3/37 • Number of events 3 • 28 weeks
|
|
Cardiac disorders
Cardiac General - Other
|
8.1%
3/37 • Number of events 4 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)
|
8.1%
3/37 • Number of events 4 • 28 weeks
|
|
Infections and infestations
Infection with unknown ANC
|
8.1%
3/37 • Number of events 3 • 28 weeks
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft Tissue - Other
|
8.1%
3/37 • Number of events 3 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Sweating (diaphoresis)
|
10.8%
4/37 • Number of events 4 • 28 weeks
|
|
Investigations
Weight loss
|
10.8%
4/37 • Number of events 4 • 28 weeks
|
|
Gastrointestinal disorders
Heartburn/dyspepsia
|
10.8%
4/37 • Number of events 4 • 28 weeks
|
|
Nervous system disorders
Taste alteration (dysgeusia)
|
10.8%
4/37 • Number of events 5 • 28 weeks
|
|
Gastrointestinal disorders
Vomiting
|
10.8%
4/37 • Number of events 5 • 28 weeks
|
|
Vascular disorders
Hemorrhage/Bleeding - Other
|
10.8%
4/37 • Number of events 7 • 28 weeks
|
|
General disorders
Rigors/chills
|
13.5%
5/37 • Number of events 5 • 28 weeks
|
|
Gastrointestinal disorders
Gastrointestinal - Other
|
13.5%
5/37 • Number of events 9 • 28 weeks
|
|
General disorders
Edema: limb
|
13.5%
5/37 • Number of events 5 • 28 weeks
|
|
Psychiatric disorders
Neurology - Other
|
13.5%
5/37 • Number of events 7 • 28 weeks
|
|
Vascular disorders
Hypotension
|
16.2%
6/37 • Number of events 8 • 28 weeks
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
16.2%
6/37 • Number of events 6 • 28 weeks
|
|
Psychiatric disorders
Insomnia
|
16.2%
6/37 • Number of events 6 • 28 weeks
|
|
Infections and infestations
Infection - Other
|
16.2%
6/37 • Number of events 8 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other
|
16.2%
6/37 • Number of events 6 • 28 weeks
|
|
Metabolism and nutrition disorders
Anorexia
|
18.9%
7/37 • Number of events 7 • 28 weeks
|
|
General disorders
Constitutional Symptoms - Other
|
21.6%
8/37 • Number of events 23 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.6%
8/37 • Number of events 8 • 28 weeks
|
|
Gastrointestinal disorders
Nausea
|
27.0%
10/37 • Number of events 11 • 28 weeks
|
|
Nervous system disorders
Dizziness
|
27.0%
10/37 • Number of events 10 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other
|
29.7%
11/37 • Number of events 19 • 28 weeks
|
|
Blood and lymphatic system disorders
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe
|
29.7%
11/37 • Number of events 14 • 28 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
29.7%
11/37 • Number of events 11 • 28 weeks
|
|
Investigations
Leukocytes (total WBC)
|
32.4%
12/37 • Number of events 34 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
32.4%
12/37 • Number of events 17 • 28 weeks
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
32.4%
12/37 • Number of events 19 • 28 weeks
|
|
Blood and lymphatic system disorders
Hemoglobin
|
43.2%
16/37 • Number of events 29 • 28 weeks
|
|
Investigations
Neutrophils/granulocytes (ANC/AGC)
|
45.9%
17/37 • Number of events 29 • 28 weeks
|
|
General disorders
Injection site reaction/extravasation changes
|
45.9%
17/37 • Number of events 20 • 28 weeks
|
|
Investigations
Platelets
|
48.6%
18/37 • Number of events 43 • 28 weeks
|
|
Gastrointestinal disorders
Diarrhea
|
48.6%
18/37 • Number of events 24 • 28 weeks
|
|
General disorders
Pain
|
51.4%
19/37 • Number of events 36 • 28 weeks
|
|
Gastrointestinal disorders
Constipation
|
54.1%
20/37 • Number of events 22 • 28 weeks
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
56.8%
21/37 • Number of events 24 • 28 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place