A Phase 1 Study of Lenalidomide Maintenance Following Allogeneic Hematopoietic Cell Transplantation in Patients With Select High Risk Hematological Malignancies
Overview
- Phase
- Phase 1
- Intervention
- Laboratory Biomarker Analysis
- Conditions
- Adult Acute Myeloid Leukemia in Remission
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 17
- Locations
- 1
- Primary Endpoint
- MTD of lenalidomide after allogeneic hematopoietic stem cell transplantation graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This phase I clinical trial is studying the side effects and the best dose of lenalidomide after donor bone marrow transplant in treating patients with high-risk hematologic cancer. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the maximal-tolerable dose (MTD) of lenalidomide after allogeneic hematopoietic stem cell transplantation (AHSCT) in patients with advanced acute myeloid leukemia (AML), non-Hodgkin's lymphoma (NHL), or chronic lymphocytic leukemia (CLL). II. Define the qualitative and quantitative toxicities of lenalidomide in regard to organ specificity, time course, predictability, and reversibility following AHSCT in these patients. SECONDARY OBJECTIVES: I. Determine the anti-tumor response in patients treated with lenalidomide after AHSCT when compared with historical controls. II. Evaluate the plasma and cellular pharmacokinetics of lenalidomide in patients enrolled on this study and interactions with supportive agents such as calcineurin inhibitors. III. Evaluate the frequency of acute and chronic graft-vs-host disease and graft failure in patients enrolled on this study. IV. Prospectively assess the feasibility of administering an oral agent post-transplant as measured by efficiency of patients being registered to therapy early and also meeting eligibility criteria for lenalidomide treatment. V. Perform pharmacodynamic studies following lenalidomide treatment including development of B, T, and myeloid cell chimerism; assessment of immune activation; cytokines; tumor cell expression of co-stimulatory molecules; development of anti-tumor antibodies and immunoglobulin recovery; and re-expression of microRNAs that may mediate lenalidomide anti-tumor effect. OUTLINE: This is a multicenter, dose-escalation study. Patients are stratified according to diagnosis (high-risk acute myeloid leukemia vs non-Hodgkin lymphoma vs high-risk chronic lymphocytic leukemia, small lymphocytic lymphoma, or B-prolymphocytic leukemia). Patients receive oral lenalidomide once daily on days 1-28. Courses repeat every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Patients undergo blood and bone marrow biopsies and aspirate collection at baseline and periodically during study for pharmacokinetic and pharmacodynamic studies. Buccal swab samples are also collected at baseline and analyzed for genetic polymorphisms. After completion of study therapy, patients are followed up for up to 1 year.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed hematologic malignancy meeting 1 of the following criteria:
- •High-risk acute myeloid leukemia meeting 1 the following criteria:
- •First complete response (CR) and ≥ 60 years of age OR \< 60 years of age with high-risk cytogenetics as defined by CALGB OR high-molecular risk and not eligible or willing to undergo myeloablative conditioning
- •Second or later complete remission
- •Not in remission but with \< 5% blasts within 3 weeks of start of conditioning chemotherapy for allogeneic transplantation
- •Patients with a history of CNS involvement allowed provided disease is in remission at the time of transplantation
- •Patients with non-Hodgkin lymphoma who are candidates for allogeneic stem cell transplantation will be eligible; patients who have relapsed status post autologous transplantation are eligible as long as they demonstrate chemotherapy sensitive disease; patients with a history of CNS involvement are eligible if this aspect of the disease is in remission at the time of transplantation
- •High-risk chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or primary and secondary B-prolymphocytic leukemia (PLL) meeting 1 of the following criteria:
- •del(17p13.1) disease that has been treated (may have been given as consolidation therapy)
- •Less than PR to chemoimmunotherapy or relapsed within 2 years of treatment
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (lenalidomide)
Patients receive oral lenalidomide once daily on days 1-28. Courses repeat every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Patients undergo blood and bone marrow biopsies and aspirate collection at baseline and periodically during study for pharmacokinetic and pharmacodynamic studies. Buccal swab samples are also collected at baseline and analyzed for genetic polymorphisms.
Intervention: Laboratory Biomarker Analysis
Treatment (lenalidomide)
Patients receive oral lenalidomide once daily on days 1-28. Courses repeat every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Patients undergo blood and bone marrow biopsies and aspirate collection at baseline and periodically during study for pharmacokinetic and pharmacodynamic studies. Buccal swab samples are also collected at baseline and analyzed for genetic polymorphisms.
Intervention: Lenalidomide
Treatment (lenalidomide)
Patients receive oral lenalidomide once daily on days 1-28. Courses repeat every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Patients undergo blood and bone marrow biopsies and aspirate collection at baseline and periodically during study for pharmacokinetic and pharmacodynamic studies. Buccal swab samples are also collected at baseline and analyzed for genetic polymorphisms.
Intervention: Pharmacological Study
Outcomes
Primary Outcomes
MTD of lenalidomide after allogeneic hematopoietic stem cell transplantation graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Time Frame: Up to day 28
Secondary Outcomes
- Overall response in patients treated with lenalidomide according to the International Working Group (IWG) criteria(Up to day 365)