Clinical Trials /

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

NCT02255162

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Lenalidomide in Combination With Microtransplantation as Post-remission Therapy in AML
  • Official Title: Safety and Feasibility of Lenalidomide in Combination With HLA-mismatched Stem-cell Microtransplantation as Post-remission Therapy in Patients With Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: 14-265
  • NCT ID: NCT02255162

Conditions

  • Acute Myeloid Leukemia (AML)
  • Acute Myelocytic Leukemia
  • Acute Myelogenous Leukemia
  • Acute Granulocytic Leukemia
  • Acute Non-Lymphocytic Leukemia

Interventions

DrugSynonymsArms
LenalidomideRevlimid®Lenalidomide
CytarabineCytosar-U ®, 1-β-Arabinofuranosylcytosine, Arabinosylcytosine, Cytosine arabinoside, Ara-CLenalidomide

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
LenalidomideExperimentalDose 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
  • Lenalidomide
  • Cytarabine

Eligibility Criteria

        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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) of lenalidomide after microtransplantation
Time Frame:Baseline, 42 Days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease Free Survival
Time Frame:1 year
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:1 Year
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:To identify incidence and severity of acute and chronic graft versus host disease (GVHD).
Time Frame:2 Years
Safety Issue:
Description:
Measure:To detect and categorize, according to severity, the cumulative incidences of toxicities
Time Frame:2 Years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Acute Myeloid Leukemia (AML)
  • Acute Myelocytic Leukemia
  • Acute Myelogenous Leukemia
  • Acute Granulocytic Leukemia
  • Acute Non-Lymphocytic Leukemia

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