Safety and Feasibility of Lenalidomide in Combination With HLA-mismatched Stem-cell Microtransplantation as Post-remission Therapy in Patients With Acute Myeloid Leukemia (AML)
Overview
- Phase
- Phase 1
- Intervention
- Lenalidomide
- Conditions
- Acute Myeloid Leukemia (AML)
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- Maximum Tolerated Dose (MTD) of lenalidomide after microtransplantation
- Status
- Terminated
- Last Updated
- 8 years ago
Overview
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
Investigators
Amir Fathi
Principal Investigators
Massachusetts General Hospital
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-
- •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.
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.
Arms & Interventions
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
Intervention: Lenalidomide
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
Intervention: HLA-mismatched stem-cell Microtransplantation
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
Intervention: Cytarabine
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) of lenalidomide after microtransplantation
Time Frame: Baseline, 42 Days
Secondary Outcomes
- 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)
- Disease Free Survival(1 year)
- Overall Survival(1 Year)
- 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)