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Phase 1-2 of Azacitidine + Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML)

This study has been completed.
Celgene Corporation
Information provided by (Responsible Party):
Bruno C. Medeiros, Stanford University Identifier:
First received: April 28, 2009
Last updated: October 13, 2014
Last verified: October 2014

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.

Condition Intervention Phase
Acute Myeloid Leukemia (AML)
Adult Acute Myeloblastic Leukemia
Drug: Lenalidomide
Drug: Azacitidine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1-2 Study of Azacitidine in Combination With Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia

Resource links provided by NLM:

Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Compete Remission (CR) Rate [ Time Frame: 12 months ]
    CR includes subjects with CR but incomplete recovery of blood counts (CRi). Responses were assessed according to the European LeukemiaNet (ELN) guidelines.

Secondary Outcome Measures:
  • 4-week Survival Rate [ Time Frame: 28 days ]
    "Early death" was assessed as death within 28 days of the start of treatment

  • Maximum Tolerated Dose (MTD) of Lenalidomide [ Time Frame: 15 months ]
    The MTD of lenalidomide was determined in study phase I, for use in study Phase II.

  • Remission Duration [ Time Frame: 26 months ]
    Responses and remission were assessed according to the ELN guidelines.

  • Overall Response Rate (ORR) [ Time Frame: 26 months ]
    ORR includes subjects with CR, CRi, and partial response (PR). Responses were assessed according to the ELN guidelines.

  • Overall Survival (OS) [ Time Frame: 88 weeks (median) ]
    OS from the start of treatment was assessed at a median follow up of 88 weeks from the end of treatment (range, 1-120), and was censored at 1 April 2012.

  • Time to CR [ Time Frame: 18 weeks ]
    CR includes subjects with CR but incomplete recovery of blood counts (CRi). Responses were assessed according to the ELN guidelines.

  • Time to PR [ Time Frame: 36 weeks ]
    Responses were assessed according to the ELN guidelines.

  • OS of Responders [ Time Frame: 88 weeks (median) ]
    OS from the start of treatment of responders (per ELN guidelines) was assessed at a median follow up of 88 weeks from the end of treatment (range, 1-120), and was censored at 1 April 2012.

Enrollment: 45
Study Start Date: April 2009
Study Completion Date: June 2012
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azacitidine followed by lenalidomide
Dose escalation then dose expansion
Drug: Lenalidomide
5 mg, 10 mg, 25 mg, and/or 50 mg of lenalidomide administered PO from day 8 to Day 28 of each cycle
Other Names:
  • CC-5013
  • Revlimid
Drug: Azacitidine
75 mg/m2 Azacitidine administered intravenously (IV) or subcutaneously (SC) for days 1 to 7 of each cycle
Other Names:
  • 5-azacytidine
  • Vidaza

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.


Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: NCT00890929

United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Celgene Corporation
Principal Investigator: Bruno Carneiro de Medeiros Stanford University
Principal Investigator: Daniel Aaron Pollyea Stanford University
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Bruno C. Medeiros, Assistant Professor, Stanford University Identifier: NCT00890929     History of Changes
Other Study ID Numbers: IRB-15611
SU-04242009-2385 ( Other Identifier: Stanford University )
RV-AML-0410 ( Other Identifier: Celgene Corporation )
HEMAML0011 ( Other Identifier: OnCore )
Study First Received: April 28, 2009
Results First Received: October 13, 2014
Last Updated: October 13, 2014

Keywords provided by Stanford University:
Acute myeloid leukemia
Acute myeloblastic leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors processed this record on May 22, 2017