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

May 16, 2018 updated by: Bruno C. Medeiros, Stanford University

A Phase 1-2 Study of Azacitidine in Combination With Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia

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.

Study Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • Vidaza
  • 5-azacytidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compete Remission (CR) Rate
Time Frame: 12 months
Compete Remission (CR) includes subjects with CR but incomplete recovery of blood counts (CRi). CR was assessed according to the European LeukemiaNet (ELN) guidelines, and is defined as the absence of clonal lymphocytes in the peripheral blood.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
4-week Survival Rate
Time Frame: 28 days
"Early death" was assessed as death within 28 days of the start of treatment
28 days
Maximum Tolerated Dose (MTD) of Lenalidomide
Time Frame: 15 months
The maximum tolerated dose (MTD) of lenalidomide was determined in study phase 1, for use in study Phase 2 (not conducted). The outcome is reported as the dose of lenalidomide that represents the MTD.
15 months
Remission Duration
Time Frame: 26 months
Responses and remission were assessed according to the ELN guidelines.
26 months
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.
26 months
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.
88 weeks (median)
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.
18 weeks
Time to PR
Time Frame: 36 weeks
Responses were assessed according to the ELN guidelines.
36 weeks
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.
88 weeks (median)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Stanford University

Collaborators

Celgene Corporation

Investigators

  • Principal Investigator: Daniel Aaron Pollyea, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (ACTUAL)

June 1, 2011

Study Completion (ACTUAL)

June 1, 2012

Study Registration Dates

First Submitted

April 28, 2009

First Submitted That Met QC Criteria

April 29, 2009

First Posted (ESTIMATE)

April 30, 2009

Study Record Updates

Last Update Posted (ACTUAL)

June 18, 2018

Last Update Submitted That Met QC Criteria

May 16, 2018

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-15611
  • SU-04242009-2385 (OTHER: Stanford University)
  • RV-AML-0410 (OTHER: Celgene Corporation)
  • HEMAML0011 (OTHER: OnCore)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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