Trial Outcomes & Findings for Azacitidine and Lenalidomide for Relapsed and Refractory Patients With Acute Myeloid Leukemia (NCT NCT01743859)

NCT ID: NCT01743859

Last Updated: 2019-10-08

Results Overview

Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 37 participants
• Primary outcome timeframe: Interim assessment after 18 patients (estimated 2 years) and full assessment after 37 patients (estimated 3-4 years)
• Results posted on: 2019-10-08

Participant Flow

Participant milestones

Measure	Azacitidine + Lenalidomide + Off Therapy Patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. Afterwards beginning on Day 8 patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. They will then enter a 2 week observation period where they will be monitored and assessed.
Overall Study STARTED	37
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Azacitidine and Lenalidomide for Relapsed and Refractory Patients With Acute Myeloid Leukemia

Baseline characteristics by cohort

Measure	Azacitidine + Lenalidomide + Off Therapy n=37 Participants Patients will receive 7 days of azacitidine followed by 3 weeks of lenalidomide. They will then have 2 weeks off therapy, for a maximum of 12 cycles. Azacitidine: Enrolled patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. Lenalidomide: Beginning on day 8, patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. Off Therapy: 2 weeks off therapy, then begin sequence again for 12 weeks.
Age, Categorical <=18 years	1 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	30 Participants n=5 Participants
Age, Continuous	73 years STANDARD_DEVIATION 5 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants
Region of Enrollment United States	37 participants n=5 Participants

PRIMARY outcome

Timeframe: Interim assessment after 18 patients (estimated 2 years) and full assessment after 37 patients (estimated 3-4 years)

Population: Relapsed/refractory AML patients who received azacitidine and lenalidomide

Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Outcome measures

Measure	Azacitidine + Lenalidomide + Off Therapy n=37 Participants Patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. Afterwards beginning on Day 8 patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. They will then enter a 2 week observation period where they will be monitored and assessed.
Percentage of Participants With Complete Remission or Complete Remission With Incomplete Recovery Blood Counts	11 percentage of participants

PRIMARY outcome

Timeframe: Planned assessment after enrollment of all 37 patients (estimated 3-4 years)

Population: relapsed/refractory patients who received azacitidine and lenaldiomide

Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination

Outcome measures

Measure	Azacitidine + Lenalidomide + Off Therapy n=37 Participants Patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. Afterwards beginning on Day 8 patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. They will then enter a 2 week observation period where they will be monitored and assessed.
Overall Response Rate	52 percentage of participants

SECONDARY outcome

Timeframe: Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years

Population: Relapsed and refractory AML patients who received azacitidine and lenalidomide

Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination

Outcome measures

Measure	Azacitidine + Lenalidomide + Off Therapy n=37 Participants Patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. Afterwards beginning on Day 8 patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. They will then enter a 2 week observation period where they will be monitored and assessed.
Response or Remission Duration	125 days Interval 23.0 to 308.0

SECONDARY outcome

Timeframe: Will begin assessment with first patient and will continue until completion of study, estimated to be 4 years

Population: Relapsed and refractory AML patients who received azacitidine and lenalidomide -See toxicity data reported for results

Change in baseline to end of study. To be measured based on Common Terminology Criteria for Adverse Events (CTCAE) criteria

Outcome measures

Measure	Azacitidine + Lenalidomide + Off Therapy n=37 Participants Patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. Afterwards beginning on Day 8 patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. They will then enter a 2 week observation period where they will be monitored and assessed.
Toxicity and SAEs Related to Treatment	46 percentage of SAEs related to treatment

SECONDARY outcome

Timeframe: Depending on outcomes, will begin assessment at 2 years and will continue until completion of study, estimated to be at four years

Population: Relapsed and refractory AML patients who received azacitidine and lenalidomide

Change in baseline to end of study

Outcome measures

Measure	Azacitidine + Lenalidomide + Off Therapy n=37 Participants Patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. Afterwards beginning on Day 8 patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. They will then enter a 2 week observation period where they will be monitored and assessed.
Overall Survival	166 days Interval 35.0 to 355.0

SECONDARY outcome

Timeframe: Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years

Population: Relapsed and refractory AML patients who received azacitidine and lenalidomide

Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination

Outcome measures

Measure	Azacitidine + Lenalidomide + Off Therapy n=37 Participants Patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. Afterwards beginning on Day 8 patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. They will then enter a 2 week observation period where they will be monitored and assessed.
Progression-free Survival	112 days Interval 33.0 to 355.0

SECONDARY outcome

Timeframe: Three years after initiating study

Population: Relapsed and refractory AML patients who received azacitidine and lenalidomide.

Change in baseline to end of study. Planned assessments of methylation changes and other biomarkers. Computational biology modeling used to identify biomarkers and predict response.

Outcome measures

Measure	Azacitidine + Lenalidomide + Off Therapy n=37 Participants Patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. Afterwards beginning on Day 8 patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. They will then enter a 2 week observation period where they will be monitored and assessed.
Determine Biomarkers That Predict Response/Toxicity	9 patients w/response predictor mutations

Adverse Events

Azacitidine + Lenalidomide + Off Therapy

Serious events: 24 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Azacitidine + Lenalidomide + Off Therapy n=37 participants at risk Patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. Afterwards beginning on Day 8 patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. They will then enter a 2 week observation period where they will be monitored and assessed.
Blood and lymphatic system disorders Febrile Neutropenia	29.7% 11/37
Gastrointestinal disorders Clostridium Defficile	5.4% 2/37
Infections and infestations Sepsis	5.4% 2/37
Cardiac disorders Syncope	5.4% 2/37
Infections and infestations Pneuomonia	5.4% 2/37
Respiratory, thoracic and mediastinal disorders Pneumothorax	2.7% 1/37
Respiratory, thoracic and mediastinal disorders Hypoxia	5.4% 2/37
Cardiac disorders Hypertension	5.4% 2/37

Other adverse events

Measure	Azacitidine + Lenalidomide + Off Therapy n=37 participants at risk Patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone. Afterwards beginning on Day 8 patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28. They will then enter a 2 week observation period where they will be monitored and assessed.
Blood and lymphatic system disorders Neutropenia	56.8% 21/37
Blood and lymphatic system disorders Thrombocytopenia	32.4% 12/37
Respiratory, thoracic and mediastinal disorders Dyspnea	45.9% 17/37
General disorders Fatigue	75.7% 28/37
Gastrointestinal disorders Nausea	43.2% 16/37
Gastrointestinal disorders Constipation	45.9% 17/37
Gastrointestinal disorders Diarrhea	56.8% 21/37
Blood and lymphatic system disorders Anemia	40.5% 15/37

Additional Information

Dr. Daniel Pollyea

University of Colorado

Email: daniel.pollyea@ucdenver.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place