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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Colorado, Denver
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01743859
First received: November 16, 2012
Last updated: May 6, 2014
Last verified: May 2014
  Purpose

Acute myeloid leukemia (AML) patients with relapsed and refractory disease have very poor outcomes. Sequential azacitidine and lenalidomide was recently shown by the PI of this study to be well-tolerated and effective in elderly, treatment naïve AML patients. Observations from this study and others that have piloted this combination have suggested that patients who received and failed prior treatments may also respond to this regimen. Therefore, the sequential combination of azacitidine with lenalidomide could potentially improve outcomes for relapsed and refractory AML patients by providing them with a treatment option that is tolerable and potentially clinically synergistic. To determine the efficacy of this combination in this population, we will pilot this phase 2 study.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Azacitidine
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sequential Treatment With Azacitidine and Lenalidomide for Relapsed and Refractory Patients With Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Complete remission or complete remission with incomplete recovery blood counts [ Time Frame: Interim assessment after 18 patients (estimated 2 years) and full assessment after 37 patients (estimated 3-4 years) ] [ Designated as safety issue: No ]
    Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination

  • Overall response rate [ Time Frame: Planned assessment after enrollment of all 37 patients (estimated 3-4 years) ] [ Designated as safety issue: No ]
    Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination


Secondary Outcome Measures:
  • Response or remission duration [ Time Frame: Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years ] [ Designated as safety issue: No ]
    Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination

  • Determine the toxicity profile for this population in this regimen [ Time Frame: Will begin assessment with first patient and will continue until completion of study, estimated to be 4 years ] [ Designated as safety issue: Yes ]
    Change in baseline to end of study. To be measured based on Common Terminology Criteria for Adverse Events (CTCAE) criteria

  • overall survival [ Time Frame: Depending on outcomes, will begin assessment at 2 years and will continue until completion of study, estimated to be at four years ] [ Designated as safety issue: No ]
    Change in baseline to end of study

  • progression-free survival [ Time Frame: Depending on outcomes, will initiate this assessment after 2 years and will continue until completion of study, estimated at 4 years ] [ Designated as safety issue: No ]
    Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination

  • Determine biomarkers that predict response/toxicity [ Time Frame: Three years after initiating study ] [ Designated as safety issue: No ]
    Change in baseline to end of study. Planned assessments of methylation changes and other biomarkers


Estimated Enrollment: 37
Study Start Date: December 2012
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Azacitidine and Lenalidomide
Patients will receive 7 days of azacitidine followed by 3 weeks of lenalidomide followed by 2 weeks off therapy for a maximum of 12 cycles
Drug: Azacitidine
Enrolled patients will receive 75 mg/m2 of azacitidine subcutaneously (SC) or intravenously (IV) on days 1-7 alone.
Other Name: Vidaza (TM)
Drug: Lenalidomide
Beginning on day 8, patients will receive 50 mg of lenalidomide PO, and will take this daily from day 8 through 28.
Other Name: Revlimid (TM)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • • World Health Organization (WHO)-confirmed AML, other than Acute Promyelocytic Leukemia (APL)

    • Age >18 years
    • White blood cell count (WBC) at initiation of treatment ≤ 10,000/L

      o If WBC is > 10,000/L patients may be started on an appropriate dose of hydroxyurea (to be determined by the investigators), until WBC < 10,000/L, at which time the hydroxyurea will be discontinued for 12 hours prior to enrollment

    • Relapsed or refractory (resistant) disease, as defined by standard criteria21:

      • Relapsed: Bone marrow blasts ≥5%; reappearance of blasts in the blood; development of extramedullary disease
      • Refractory (resistant): Failure to achieve Complete Remission (CR) or complete remission with incomplete recovery of blood counts (CRi) in patients who survive ≥7 days following completion of initial treatment, with evidence of persistent leukemia by blood and/or bone marrow examination
    • Failure of at least one prior therapy
    • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (See Appendix D: ECOG Performance Status Scale)
    • Life expectancy > 2 months
    • All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist® (RevAssist is a restricted distribution program for receiving lenalidomide)
    • Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 million International Units per milliliter (mIU/mL) 10 - 14 days prior to study enrollment and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to 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 she starts taking lenalidomide. FCBP 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. See Appendix F: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods
    • 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:

  • • Known or suspected hypersensitivity to azacitidine or mannitol

    • Patients with advanced malignant hepatic tumors.
    • Treatment less than four weeks prior to enrollment with other experimental therapies or antineoplastic agents, with the exception of hydroxyurea
    • Inability to swallow or absorb drug
    • Prior treatment with lenalidomide for AML
    • 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
    • Significant uncontrolled cardiac arrhythmias
    • Uncontrolled psychiatric illness that would limit compliance with requirements
    • Known Human immunodeficiency virus (HIV) infection
    • Graft vs. host disease ≥ grade 2
    • Relapse after allogeneic stem cell transplantation prior to post-transplant day 30
    • Pregnant or breast feeding females; lactating females must agree not to breast feed 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:

      • Either creatinine >2.0 mg/dL or creatinine clearance <30 mL/min
      • Total bilirubin > 2 x institutional upper limit of normal (ULN) (unless documented Gilbert's syndrome)
      • Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) > 3 x institutional ULN
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01743859

Contacts
Contact: Nicole Ayodeji, BSN 720-848-0701 Nikki.Ayodeji@ucdenver.edu
Contact: Leigh Walzer, BS, BSN, RN 720-848-0736 Leigh.Walzer@ucdenver.edu

Locations
United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Daniel Pollyea, MD         
Sub-Investigator: Jonathan Gutman, MD         
Sponsors and Collaborators
University of Colorado, Denver
Celgene Corporation
Investigators
Principal Investigator: Daniel Pollyea, MD University of Colorado, Denver
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01743859     History of Changes
Other Study ID Numbers: 12-1283.cc, NCI-2012-03191
Study First Received: November 16, 2012
Last Updated: May 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Colorado, Denver:
Myeloid
Leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Azacitidine
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014