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Azacitidine + Lenalidomide Combo in the Elderly With Previously Treated AML & High-Risk MDS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01442714
Recruitment Status : Terminated (Lack of efficacy - Inability to meet the primary response endpoint)
First Posted : September 28, 2011
Results First Posted : January 3, 2018
Last Update Posted : January 3, 2018
Celgene Corporation
Information provided by (Responsible Party):
Bruno C. Medeiros, Stanford University

Brief Summary:
The purpose of the trial is to study how the elderly patients who have previously undergone treatment for acute myeloid leukemia and high-rRisk myelodysplastic syndromes, respond to a combined treatment with azacitidine and lenalidomide.

Condition or disease Intervention/treatment Phase
Leukemia Acute Myeloid Leukemia (AML) Myelodysplastic Syndromes (MDS) Drug: Azacitidine Drug: Lenalidomide Phase 2

Detailed Description:

This is an open label, single-center, and phase 2 study of the combination of azacitidine with lenalidomide in previously treated elderly patients with acute myeloid leukemia (AML) and/or high-risk myelodysplastic syndrome (MDS) who have failed prior therapy with either a demethylating agent and/or IMIDs. MDS includes Chronic Myeloid Leukemia (CML).

Participants patients will receive azacitidine on the first 7 days followed by lenalidomide. Disease assessments with bone marrow examinations will be performed and if a complete response (CR); Complete remission with incomplete count recovery (CRi); partial response (PR); or stable disease (SD) is documented after 6 total cycles, participants will continue treatment until evidence of disease progression, provided they are tolerating treatment. Participants who have progressive disease or relapsed disease after the 6th cycle will be taken off the study, and participants with excessive toxicity at any time will be taken off the study.

  • CR = Less than 5% blasts with no Auer rods, absence of extramedullary disease, absolute neutrophil count (ANC) > 1000/µL, platelets > 100,000/µL, and independence of red cell transfusion)
  • CR with incomplete recovery (CRi) = all criteria of a CR with the exception of a platelet count less than 100,000/µL or residual neutropenia (< 1000/µL).
  • PR = Meeting all hematologic criteria for CR with an allowance for 5% to 25% bone marrow blasts or decrease of pretreatment bone marrow blast percentage by ≥ 50%.
  • SD = Change in bone marrow aspirate blast count within 10% of baseline.
  • PD = Progressive / relapsed disease defined as reappearance of blasts in the blood or bone marrow blasts ≥ 5%, and development of extramedullary disease.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Azacitidine Plus Lenalidomide Combination in Elderly Patients With Previously Treated Acute Myeloid Leukemia (AML) & High-Risk Myelodysplastic Syndromes (MDS) (VIREL2 Trial)
Study Start Date : August 2011
Actual Primary Completion Date : March 2014
Actual Study Completion Date : May 2014

Arm Intervention/treatment
Experimental: Azacitidine plus Lenalidomide
Patients will receive a single dose of azacitidine 75 mg/m² SC or IV on days 1 to 7, followed by lenalidomide 50 mg PO daily on days 8 to 28 of a 42-day cycle.
Drug: Azacitidine
Azacitidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine is thought to induce antineoplastic activity via two mechanisms; inhibition of DNA methyltransferase at low doses, causing hypomethylation of DNA, and direct cytotoxicity in abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA at high doses, resulting in cell death
Other Names:
  • 5-azacytidine
  • Vidaza

Drug: Lenalidomide
Lenalidomide has been used to successfully treat both inflammatory disorders and cancers. In vitro, lenalidomide has three main activities: direct anti-tumor effect, inhibition of angiogenesis, and immunomodulatory role. In vivo, lenalidomide induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory activity.
Other Names:
  • CC-5013
  • Celgene
  • Revlimid

Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 203 days ]
    Overall response rate was defined as the sum of Complete Response (CR) + CR with incomplete count recovery (CRi) + Partial Response (PR).

Secondary Outcome Measures :
  1. Median Duration of Response [ Time Frame: 203 days ]
    The median duration of response was defined by the median duration of response for participants with Complete Response (CR); CR with incomplete count recovery (CRi); or Partial Response (PR).

  2. Overall Survival [ Time Frame: 462 Days ]
    Survival was measured from the 1st day of azacitidine treatment to death from any cause.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  • acute myeloid leukemia (AML) (according to the WHO 2008 classification):

    • De novo
    • Secondary AML previously treated with demethylating agents for AML
    • Secondary AML previously treated with demethylating agents for MDS
    • Secondary AML previously treated with high dose lenalidomide for AML (≥ 25mg)
  • High Risk MDS:

    • Del (5q)
    • Non-del (5q), previously-treated with lenalidomide.
    • Novo or secondary HR-MDS previously treated with demethylating agents
  • White blood cell (WBC) ≤ 10,000
  • Age ≥ 60
  • Not an immediate candidate for allogeneic stem cell transplantation
  • Unwilling or unable to receive conventional chemotherapy
  • Prior therapy:

    • with single agent demethylator (5-Azacitidine or Decitabine)
    • with Lenalidomide
  • Eastern Cooperative Oncology Group performance status ≤ 2
  • Life expectancy > 2 months
  • All study participants must be registered into the mandatory RevAssist program
  • Willing and able to comply with the requirements of RevAssist
  • Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test 10-14 days prior to study enrollment and again within 24 hours of prescribing lenalidomide

    • Must commit to either continued abstinence from intercourse or begin two acceptable methods of birth control, at least 28 days before she starts taking lenalidomide.
    • Must also agree to ongoing pregnancy testing.
  • Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
  • Willing and able to understand and voluntarily sign a written informed consent
  • Able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

  • Patients with LR-MDS progressing to HR-MDS after low dose lenalidomide or 5-day azacitidine will not be eligible.
  • History of intolerance to thalidomide

    -development of erythema nodosum while taking thalidomide or similar drugs

  • Known or suspected hypersensitivity to azacitidine or mannitol
  • Patients with advanced malignant hepatic tumors.
  • Concomitant treatment with other anti-neoplastic agents, with the exception of hydroxyurea
  • Previous participation on the VIREL study with the concomitant use of azacitidine plus lenalidomide.
  • Anti-neoplastic treatment less than four weeks prior to enrollment, with the exception of 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
  • Pregnant
  • Breast feeding
  • Lactating females must agree not to breast feed while taking lenalidomide
  • Other medical or psychiatric illness or organ dysfunction or laboratory abnormality
  • Laboratory abnormalities:

    • Either creatinine ≥ 1.5 mg / dL or creatinine clearance ≤ 50 mL / min
    • Total bilirubin >1.5 x institutional ULN
    • AST and ALT > 2.5 x institutional ULN

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01442714

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United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Celgene Corporation
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Principal Investigator: Bruno Carneiro de Medeiros Stanford University
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Responsible Party: Bruno C. Medeiros, Associate Professor Medicine Hematology, Stanford University Identifier: NCT01442714    
Other Study ID Numbers: IRB-21686
SU-08122011-8268 ( Other Identifier: Stanford University )
HEM0022 ( Other Identifier: OnCore Number )
VIREL2 ( Other Identifier: Stanford University )
First Posted: September 28, 2011    Key Record Dates
Results First Posted: January 3, 2018
Last Update Posted: January 3, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors