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

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ClinicalTrials.gov Identifier: NCT01254578
Recruitment Status : Completed
First Posted : December 6, 2010
Last Update Posted : September 25, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE December 3, 2010
First Posted Date  ICMJE December 6, 2010
Last Update Posted Date September 25, 2017
Actual Study Start Date  ICMJE November 24, 2010
Actual Primary Completion Date November 9, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2013)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 3, 2010)
Maximal-tolerable dose (MTD) of lenalidomide after allogeneic hematopoietic stem cell transplantation
Change History Complete list of historical versions of study NCT01254578 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2012)
Overall response in patients treated with lenalidomide according to the International Working Group (IWG) criteria [ Time Frame: Up to day 365 ]
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 3, 2010)
Overall response in patients treated with lenalidomide
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Lenalidomide After Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancers
Official Title  ICMJE A Phase 1 Study of Lenalidomide Maintenance Following Allogeneic Hematopoietic Cell Transplantation in Patients With Select High Risk Hematological Malignancies
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
  • Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11
  • Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1
  • Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A
  • Adult Acute Promyelocytic Leukemia With PML-RARA
  • Adult Grade III Lymphomatoid Granulomatosis
  • Adult Nasal Type Extranodal NK/T-Cell Lymphoma
  • Alkylating Agent-Related Acute Myeloid Leukemia
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-Cell Lymphoma
  • Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
  • Hepatosplenic T-Cell Lymphoma
  • Intraocular Lymphoma
  • Lymphomatous Involvement of Non-Cutaneous Extranodal Site
  • Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
  • Nodal Marginal Zone Lymphoma
  • Post-Transplant Lymphoproliferative Disorder
  • Primary Cutaneous B-Cell Non-Hodgkin Lymphoma
  • Prolymphocytic Leukemia
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Grade III Lymphomatoid Granulomatosis
  • Recurrent Adult Immunoblastic Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Adult T-Cell Leukemia/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 and Sezary Syndrome
  • Recurrent Non-Hodgkin Lymphoma
  • Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Hairy Cell Leukemia
  • Richter Syndrome
  • Small Intestinal Lymphoma
  • Splenic Marginal Zone Lymphoma
  • T-Cell Large Granular Lymphocyte Leukemia
  • Testicular Lymphoma
  • Waldenstrom Macroglobulinemia
Intervention  ICMJE
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Lenalidomide
    Given orally
    Other Names:
    • CC-5013
    • CC5013
    • CDC 501
    • Revlimid
  • Other: Pharmacological Study
    Correlative studies
Study Arms  ICMJE 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.

Interventions:
  • Other: Laboratory Biomarker Analysis
  • Drug: Lenalidomide
  • Other: Pharmacological Study
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 22, 2017)
17
Original Estimated Enrollment  ICMJE
 (submitted: December 3, 2010)
90
Actual Study Completion Date  ICMJE November 9, 2012
Actual Primary Completion Date November 9, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01254578
Other Study ID Numbers  ICMJE NCI-2011-02551
NCI-2011-02551 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
OSU 10079
OSU-10079
CDR0000688918
2010C0069
OSU-2010C0069
OSU 10079 ( Other Identifier: Ohio State University Comprehensive Cancer Center )
8305 ( Other Identifier: CTEP )
P30CA016058 ( U.S. NIH Grant/Contract )
U01CA076576 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Leslie Andritsos Ohio State University Comprehensive Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP