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Trial record 6 of 16 for:    LENALIDOMIDE AND Leukemia AND Azacitidine

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

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ClinicalTrials.gov Identifier: NCT00890929
Recruitment Status : Completed
First Posted : April 30, 2009
Results First Posted : October 20, 2014
Last Update Posted : June 18, 2018
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Bruno C. Medeiros, Stanford University

Tracking Information
First Submitted Date  ICMJE April 28, 2009
First Posted Date  ICMJE April 30, 2009
Results First Submitted Date  ICMJE October 13, 2014
Results First Posted Date  ICMJE October 20, 2014
Last Update Posted Date June 18, 2018
Study Start Date  ICMJE April 2009
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 29, 2009)
  • Determination of maximum tolerated dose (MTD) and adverse event profile, to be measured during Phase I
  • Complete response (CR) rate and remission duration, to be measured after Phase II
Change History Complete list of historical versions of study NCT00890929 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2018)
  • 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 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2009)
  • 30-day survival rate
  • Determination of in vivo biological interaction between azacitidine and lenalidomide using laboratory-based techniques, and correlation of these results with clinical outcomes
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 1-2 of Azacitidine + Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML)
Official Title  ICMJE A Phase 1-2 Study of Azacitidine in Combination With Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia (AML)
  • Adult Acute Myeloblastic Leukemia
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Azacitidine followed by lenalidomide
Dose escalation then dose expansion
Interventions:
  • Drug: Lenalidomide
  • Drug: Azacitidine
Publications *

*   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: August 23, 2010)
45
Original Estimated Enrollment  ICMJE
 (submitted: April 29, 2009)
18
Actual Study Completion Date  ICMJE June 2012
Actual Primary Completion Date June 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 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 NCT00890929
Other Study ID Numbers  ICMJE IRB-15611
SU-04242009-2385 ( Other Identifier: Stanford University )
RV-AML-0410 ( Other Identifier: Celgene Corporation )
HEMAML0011 ( Other Identifier: OnCore )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bruno C. Medeiros, Stanford University
Study Sponsor  ICMJE Stanford University
Collaborators  ICMJE Celgene Corporation
Investigators  ICMJE
Principal Investigator: Bruno Carneiro de Medeiros Stanford University
Principal Investigator: Daniel Aaron Pollyea Stanford University
PRS Account Stanford University
Verification Date May 2018

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