Lenalidomide After Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancers

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01254578
First received: December 3, 2010
Last updated: June 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Grade III Lymphomatoid Granulomatosis
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Post-transplant Lymphoproliferative Disorder
Prolymphocytic Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Richter Syndrome
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Waldenström Macroglobulinemia
Drug: lenalidomide
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Lenalidomide Maintenance Following Allogeneic Hematopoietic Cell Transplantation in Patients With Select High Risk Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall response in patients treated with lenalidomide according to the International Working Group (IWG) criteria [ Time Frame: Up to day 365 ] [ Designated as safety issue: No ]
    Estimated using exact binomial methods along with its confidence interval. The non-parametric Wilcoxon signed-rank procedure will be used to compare to baseline values for correlative studies.


Estimated Enrollment: 60
Study Start Date: November 2010
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Drug: lenalidomide
Given orally
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
      • Nucleoside analog refractory disease or disease that relapsed after two prior regimens
      • Patients with Richter (large cell) transformation allowed provided the large cell component of the disease is in remission (< 10% large cells in the bone marrow allowed)
  • Patient has undergone an allogeneic stem cell transplantation using a reduced-intensity or non-myeloablative conditioning regimen within the past 60 days

    • At least 40% T-cell donor chimerism at day 30
  • ECOG performance status 0-2 (Karnofsky 60-100%)
  • Life expectancy > 3 months
  • Myeloid engraftment with absolute neutrophil count > 1,000/μL and platelet count > 50,000/μL (after allogeneic hematopoietic stem cell transplantation [AHSCT])
  • Total bilirubin normal
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)

    • AST < 3 times ULN after AHSCT
  • Creatinine clearance ≥ 50 mL/min in stratum 1 or ≥ 30 mL/min in stratum 2
  • DLCO > 40% with no symptomatic pulmonary disease
  • LVEF ≥ 30% by echocardiogram or MUGA
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must agree to use two acceptable methods of contraception (one highly effective method and one additional effective method) or practice abstinence for ≥ 28 days before, during, and ≥ 28 days after completing lenalidomide
  • HIV negative
  • No uncontrolled infection requiring intravenous therapy or poorly controlled diabetes mellitus
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to lenalidomide
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • No history of grade 3 or 4 graft-vs-host disease (GVHD)

    • If patient has acute GVHD grade 1 or 2, GVHD must be controlled and dose of oral prednisone or equivalent ≤ 20 mg per day (after AHSCT)
  • More than 4 weeks since prior chemotherapy (excluding steroids), radiotherapy, or radioimmunoconjugate therapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01254578

Locations
United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: Leslie Andritsos Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01254578     History of Changes
Other Study ID Numbers: NCI-2011-02551, NCI-2011-02551, OSU-10079, CDR0000688918, 2010C0069, OSU-2010C0069, OSU 10079, 8305, P30CA016058, U01CA076576
Study First Received: December 3, 2010
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Burkitt Lymphoma
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Hairy Cell
Leukemia, Lymphoid
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Prolymphocytic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Lymphoproliferative Disorders
Waldenstrom Macroglobulinemia
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone

ClinicalTrials.gov processed this record on July 23, 2014