Clinical trial NCT00890929: Phase 1-2 of Azacitidine + Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML)
Official title: A Phase 1-2 Study of Azacitidine in Combination With Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia (AML)
Adult Acute Myeloblastic Leukemia
Keywords: Acute myeloid leukemia
Acute myeloblastic leukemia
AML
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2009-04-30
Enrollment: 45
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study has a phase 1 and a phase 2 component.

In phase 1, the objective is to determine the maximum tolerated dose (MTD) of lenalidomide when after azacitidine.

In phase 2, the objective is to determine the efficacy of the combination treatment.

Detailed description: The treatment regimen in this study is 7 day courses of azacitidine 75 mg/m2 followed by a 21-day courses of lenalidomide. For the primary objective, each 28-day cycle was repeated for a total of up to 6 cycles. Study completion was defined as 18 cycles of treatment, disease progression, or death.

In phase 1, the objective was to determine the maximum tolerated dose (MTD) of lenalidomide 5 mg, 10 mg, 25 mg or 50 mg, when administered after azacitidine.

In phase 2, the objective was to assess the efficacy of MTD lenalidomide administered after azacitidine, in up to six 28-day cycles.

Eligibility criteria: Inclusion Criteria

* WHO-confirmed acute myeloid leukemia (AML), except acute promyelocytic leukemia (APL)
* White blood cell count (WBC) at initiation of treatment ≤ 10,000

  ◦If WBC is \> 10,000 patients may be started on an appropriate dose of hydroxyurea (to be determined by the investigators), until WBC \< 10,000, at which time the hydroxyurea will be discontinued for 24 hours prior to enrollment
* Age ≥ 60 years and not a candidate for allogeneic stem cell transplantation
* Unwilling or unable to receive conventional chemotherapy
* No prior therapy, except supportive care measures such as growth factor support, blood product transfusions, apheresis, or hydroxyurea
* ECOG performance status ≤ 2
* Life expectancy \> 2 months
* All study participants must be registered into the mandatory RevAssist® program, and must be willing and able to comply with the requirements of RevAssist
* If a female of childbearing potential (FCBP):

  * Must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 to 14 days prior to study enrollment and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days)
  * Must commit to either continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control, one highly effective method and one additional effective method at the same time, at least 28 days before starting lenalidomide.
  * Must also agree to ongoing pregnancy testing.
  * Male partners must use a latex condom during sexual contact, including if the male partners has previously had a successful vasectomy.
* Able to adhere to the study visit schedule and other protocol requirements
* Willing and able to understand and voluntarily sign a written informed consent

Exclusion Criteria

* Relapsed or refractory disease
* Prior therapy with lenalidomide
* History of intolerance to thalidomide or development of erythema nodosum while taking thalidomide or similar drugs
* Known or suspected hypersensitivity to azacitidine or mannitol
* Advanced malignant hepatic tumors
* Concomitant treatment with other anti-neoplastic agents, except hydroxyurea
* Anti-neoplastic treatment less than four weeks prior to enrollment, except hydroxyurea
* Use of any other experimental drug or therapy within 28 days of baseline
* Inability to swallow or absorb drug
* Active opportunistic infection or treatment for opportunistic infection within four weeks of first day of study drug dosing
* New York Heart Association Class III or IV heart failure
* Unstable angina pectoris
* Uncontrolled cardiac arrhythmia
* Uncontrolled psychiatric illness that would limit compliance with requirements
* Known HIV infection
* If female:

  * Pregnant
  * Breast-feeding females, if they do not agree to not breastfeed while taking lenalidomide
* Other medical or psychiatric illness or organ dysfunction or laboratory abnormality which in the opinion of the investigator would compromise the patient's safety or interfere with data interpretation
* Laboratory abnormalities:

  * Creatinine ≥ 1.5 mg/dL
  * Creatinine clearance ≤ 50 mL/min
  * Total bilirubin \> 1.5 x institutional upper limit of normal (ULN), except documented Gilbert's syndrome
  * AST \> 2.5 x institutional ULN
  * ALT \> 2.5 x institutional ULN

Primary outcomes:
measure: Compete Remission (CR) Rate
timeFrame: 12 months
Secondary outcomes:
measure: 4-week Survival Rate
timeFrame: 28 days
measure: Maximum Tolerated Dose (MTD) of Lenalidomide
timeFrame: 15 months
measure: Remission Duration
timeFrame: 26 months
measure: Overall Response Rate (ORR)
timeFrame: 26 months
measure: Overall Survival (OS)
timeFrame: 88 weeks (median)
measure: Time to CR
timeFrame: 18 weeks
measure: Time to PR
timeFrame: 36 weeks
measure: OS of Responders
timeFrame: 88 weeks (median)
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Bruno Carneiro de Medeiros
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Daniel Aaron Pollyea
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pollyea DA, Zehnder J, Coutre S, Gotlib JR, Gallegos L, Abdel-Wahab O, Greenberg P, Zhang B, Liedtke M, Berube C, Levine R, Mitchell BS, Medeiros BC. Sequential azacitidine plus lenalidomide combination for elderly patients with untreated acute myeloid leukemia. Haematologica. 2013 Apr;98(4):591-6. doi: 10.3324/haematol.2012.076414. Epub 2012 Dec 14.
citation: Pollyea DA, Kohrt HE, Gallegos L, Figueroa ME, Abdel-Wahab O, Zhang B, Bhattacharya S, Zehnder J, Liedtke M, Gotlib JR, Coutre S, Berube C, Melnick A, Levine R, Mitchell BS, Medeiros BC. Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia. Leukemia. 2012 May;26(5):893-901. doi: 10.1038/leu.2011.294. Epub 2011 Oct 28.