Acute Granulocytic Leukemia, Acute Myelocytic Leukemia, Acute Myelogenous Leukemia, Acute Myeloid Leukemia (AML), Acute Non-Lymphocytic Leukemia
Conditions
Keywords
Acute Myeloid Leukemia (AML), Acute Myelocytic Leukemia, Acute Myelogenous Leukemia, Acute Granulocytic Leukemia, Acute Non-Lymphocytic Leukemia
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
Interventions
DRUGLenalidomide
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.
GENETICHLA-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.
DRUGCytarabine
Patients will receive cytarabine post-remission therapy for 3 cycles, on days 1-5 of each cycle.
Sponsors
Celgene Corporation
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose (MTD) of lenalidomide after microtransplantation | Baseline, 42 Days |
Secondary
| Measure | Time frame |
|---|---|
| Disease Free Survival | 1 year |
| Overall Survival | 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 | 2 Years |
| To identify incidence and severity of acute and chronic graft versus host disease (GVHD). | 2 Years |
| To detect and categorize, according to severity, the cumulative incidences of toxicities | 2 Years |
Countries
United States
Outcome results
None listed