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Lenalidomide in Combination With Microtransplantation as Post-remission Therapy in AML

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: NCT02255162
Recruitment Status : Terminated (Slow Accrual)
First Posted : October 2, 2014
Last Update Posted : August 18, 2017
Celgene Corporation
Information provided by (Responsible Party):
Amir Fathi, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE September 26, 2014
First Posted Date  ICMJE October 2, 2014
Last Update Posted Date August 18, 2017
Actual Study Start Date  ICMJE January 2015
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 29, 2014)
Maximum Tolerated Dose (MTD) of lenalidomide after microtransplantation [ Time Frame: Baseline, 42 Days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02255162 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 29, 2014)
  • Disease Free Survival [ Time Frame: 1 year ]
  • Overall Survival [ Time Frame: 1 Year ]
  • To assess immunomodulatory effects of this combination through measurement of T cell subsets by flow cytometric techniques and through microchimerism analysis at multiple points on study [ Time Frame: 2 Years ]
  • To identify incidence and severity of acute and chronic graft versus host disease (GVHD). [ Time Frame: 2 Years ]
  • To detect and categorize, according to severity, the cumulative incidences of toxicities [ Time Frame: 2 Years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Lenalidomide in Combination With Microtransplantation as Post-remission Therapy in AML
Official Title  ICMJE Safety and Feasibility of Lenalidomide in Combination With HLA-mismatched Stem-cell Microtransplantation as Post-remission Therapy in Patients With Acute Myeloid Leukemia (AML)
Brief Summary

This research study is evaluating the safety and tolerability of the drug lenalidomide in combination with and following mismatched related donor microtransplantation in high risk AML patients in first remission. This study also aims to define the maximum tolerated dose (MTD) of lenalidomide given in this setting.

Microtransplantation seeks to give the participant donor cells in hopes that those cells can attack the underlying cancer. However, since the donor cells do not replace all of the host cells, it can hopefully avoid many of the serious risks involved with standard transplant, including graft-vs.-host disease (GVHD) - a complication where the donor cells attack the participant's normal body. Recent studies have suggested that lenalidomide can help aid donor cells to attack cancer when given after a stem cell transplant. This trial is trying to see if lenalidomide can help encourage the attack of leukemia cells by donor cells given as part of microtransplantation.

The FDA (the U.S. Food and Drug Administration) has approved lenalidomide but it has been approved for other uses such as in the treatment of other cancers including multiple myeloma and non-Hodgkin lymphoma. Although lenalidomide has been studied in patients with AML, it has not been approved by the FDA for standard use in AML. Lenalidomide is a compound made by the Celgene Corporation. It has properties which could demonstrate antitumor effects. The exact antitumor mechanism of action of lenalidomide is unknown.

Detailed Description

After the screening procedures confirm that the participant is eligible to participate in the research study. The participant will be given a study drug-dosing calendar.

The investigators are looking for the highest dose of the study drug that can be administered safely without severe or unmanageable side effects in participants, not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well they have tolerated their doses. Participants will receive the following:

  • Cytarabine
  • Microtransplantation
  • Lenalidomide
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia (AML)
  • Acute Myelocytic Leukemia
  • Acute Myelogenous Leukemia
  • Acute Granulocytic Leukemia
  • Acute Non-Lymphocytic Leukemia
Intervention  ICMJE
  • Drug: Lenalidomide
    Patients will receive lenalidomide starting on day 6 of each post-remission cycle, following conclusion of cytarabine post-remission therapy on days 1-5. Following count recovery in the third post-remission cycle, patients will then receive lenalidomide daily as a maintenance therapy.
    Other Name: •Revlimid®
  • Genetic: HLA-mismatched stem-cell Microtransplantation
    Patient will receive HLA-mismatched stem cell microtransplant infusion on day 6 of each post-remission cycle, following conclusion of course of cytarabine in each cycle.
  • Drug: Cytarabine
    Patients will receive cytarabine post-remission therapy for 3 cycles, on days 1-5 of each cycle.
    Other Names:
    • Cytosar-U ®
    • 1-β-Arabinofuranosylcytosine
    • Arabinosylcytosine
    • Cytosine arabinoside
    • Ara-C
Study Arms  ICMJE Experimental: Lenalidomide

Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation.

Participants will receive the following:

  • Cytarabine-intravenous, fixed dosage, given 5 times during cycle
  • HLA-mismatched stem-cell microtransplantation
  • Lenalidomide-administered daily per cycle
  • Drug: Lenalidomide
  • Genetic: HLA-mismatched stem-cell Microtransplantation
  • Drug: Cytarabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 15, 2017)
Original Estimated Enrollment  ICMJE
 (submitted: September 29, 2014)
Actual Study Completion Date  ICMJE December 2016
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Recipient Inclusion Criteria
  • Adults, aged 18 through 75 years of age, with pathologically confirmed acute myelogenous leukemia, in pathologically confirmed complete remission following anti-leukemic therapy.
  • AST, ALT and Alkaline Phosphatase <5x Upper Limit normal (ULN), direct bilirubin < 2.0 mg/dl.
  • Adequate renal function as defined by: calculated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault Formula) or serum Cr less than institution ULN (the elderly will often have < 60 GFR)
  • ECOG performance status 0-2.
  • Have a diagnosis of high-risk AML as established by a poor-risk karyotype, adverse risk by ELN criteria, a therapy-related AML, age ≥ 60 or with antecedent hematologic disorder
  • LVEF must be equal to or greater than 40%, as measured by MUGA scan or echocardiogram
  • Patients, or appropriate designee, must be able to provide informed consent.
  • Must not have received systemic anti-neoplastic therapy, including radiotherapy within 14 days of study treatment.
  • Female patients of childbearing age must have negative pregnancy test.
  • Male subject agrees to use an acceptable method for contraception during the entire study treatment period and through 6 months after the last dose of lenalidomide.
  • All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. If needed, patients should be able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation.
  • Donor Inclusion Criteria
  • Haploidentical 1st-degree relative as defined by 3/6 or 4/6 HLA-matched at HLA -A, -B, or -DRB1 who is 18-70 years of age
  • ECOG performance status 0 or 1
  • Excellent health per conventional pre-donor history (medical and psychosocial evaluation)
  • No positive testing for viral infection (HbsAg, HIV, HCV)
  • Donor ability to understand and provide informed consent
  • Meets standard institutional criteria for GCSF mobilized PBSC donation

Exclusion Criteria:

  • Recipient Exclusion Criteria
  • Diagnosis of acute promyelocytic leukemia
  • Active refractory or relapsed acute leukemia
  • Prior use of fludarabine, as this agent has been associated with higher subsequent rates of graft versus host disease
  • Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.
  • Uncontrolled intercurrent illness that would limit compliance with study requirements.
  • HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with study drug. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy.
  • A diagnosis of active hepatitis B or C as defined by detectable viral load assays in the blood
  • Known hypersensitivity to thalidomide or lenalidomide.
  • The development of erythema nodosum if characterized by a desquamating rash while taking lenalidomide.
  • Significant cardiac disease as determined by the investigator including:

    • Known or suspected cardiac amyloidosis
    • Congestive heart failure of Class III or IV of the NYHA classification
    • Uncontrolled angina, hypertension or arrhythmia
    • Myocardial infarction in past 6 months
    • Any uncontrolled or severe cardiovascular disease
    • Prior cerebrovascular event with persistent neurologic deficit
  • Medical conditions that, in the investigator's opinion, would impose excessive risk to the subject.
  • Equal to or greater than grade 2 ataxia, cranial or peripheral neuropathy.
  • Systemic infection requiring IV antibiotic therapy within 7 days preceding the first dose of study drug, or other severe infection.
  • Pregnant women are excluded from this study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
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 NCT02255162
Other Study ID Numbers  ICMJE 14-265
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Amir Fathi, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE Celgene Corporation
Investigators  ICMJE
Principal Investigator: Amir Fathi, MD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date August 2017

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