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Trial record 8 of 53 for:    LENALIDOMIDE AND Leukemia AND Acute Myeloid Leukemia (AML)

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

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.
 
ClinicalTrials.gov Identifier: NCT01743859
Recruitment Status : Completed
First Posted : December 6, 2012
Results First Posted : October 8, 2019
Last Update Posted : October 8, 2019
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
University of Colorado, Denver

Tracking Information
First Submitted Date  ICMJE November 16, 2012
First Posted Date  ICMJE December 6, 2012
Results First Submitted Date  ICMJE July 5, 2019
Results First Posted Date  ICMJE October 8, 2019
Last Update Posted Date October 8, 2019
Actual Study Start Date  ICMJE December 6, 2012
Actual Primary Completion Date April 27, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2019)
  • Percentage of Participants With 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) ]
    Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
  • Overall Response Rate [ Time Frame: Planned assessment after enrollment of all 37 patients (estimated 3-4 years) ]
    Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination
Original Primary Outcome Measures  ICMJE
 (submitted: December 4, 2012)
  • 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) ]
    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) ]
    Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2019)
  • 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 ]
    Change in baseline to end of study. To be assessed by standard criteria based on bone marrow examination
  • Toxicity and SAEs Related to Treatment [ Time Frame: Will begin assessment with first patient and will continue until completion of study, estimated to be 4 years ]
    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 ]
    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 ]
    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 ]
    Change in baseline to end of study. Planned assessments of methylation changes and other biomarkers. Computational biology modeling used to identify biomarkers and predict response.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2012)
  • 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    Change in baseline to end of study. Planned assessments of methylation changes and other biomarkers
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Azacitidine and Lenalidomide for Relapsed and Refractory Patients With Acute Myeloid Leukemia
Official Title  ICMJE Sequential Treatment With Azacitidine and Lenalidomide for Relapsed and Refractory Patients With Acute Myeloid Leukemia
Brief Summary The primary objective of this study is to determine the complete remission/complete remission with incomplete recovery of blood counts (CR/CRi) rate for relapsed and refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) patients.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • 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)
  • Other: Off Therapy
    2 weeks off therapy, then begin sequence again for 12 weeks.
Study Arms  ICMJE Experimental: Azacitidine + Lenalidomide + Off Therapy
Patients will receive 7 days of azacitidine followed by 3 weeks of lenalidomide. They will then have 2 weeks off therapy, for a maximum of 12 cycles.
Interventions:
  • Drug: Azacitidine
  • Drug: Lenalidomide
  • Other: Off Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 4, 2012)
37
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 3, 2016
Actual Primary Completion Date April 27, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01743859
Other Study ID Numbers  ICMJE 12-1283.cc
NCI-2012-03191 ( Other Identifier: National Cancer Institute )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Colorado, Denver
Study Sponsor  ICMJE University of Colorado, Denver
Collaborators  ICMJE Celgene
Investigators  ICMJE
Principal Investigator: Daniel Pollyea, MD University of Colorado, Denver
PRS Account University of Colorado, Denver
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP