Lenalidomide And Rituximab as Maintenance Therapy in Treating Patients With B-Cell Non-Hodgkin Lymphoma

November 25, 2015 updated by: Case Comprehensive Cancer Center

Phase I/II Trial of Maintenance Therapy With Lenalidomide and Rituximab Following High-Dose Chemotherapy and Autologous Stem Cell Transplantation for B-cell Non-Hodgkin Lymphoma

RATIONALE: Lenalidomide may stop the growth of cancer by blocking blood flow to the tumor. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving lenalidomide together with rituximab may be an effective treatment for B-cell non-Hodgkin lymphoma.

PURPOSE: This phase I/II trial is studying the side effects and best dose of lenalidomide when given together with rituximab as maintenance therapy in treating patients with B-cell non-Hodgkin lymphoma.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The study was originally intended to be Phase I/Phase II but it terminated early because of toxicity of treatment and therefore never moved to the Phase II portion of the study.

PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) and safety of lenalidomide in combination with rituximab in subjects with B-cell NHL following ASCT. (Phase I) II. To evaluate the tolerability of maintenance therapy with lenalidomide and rituximab after ASCT in subjects with B-cell NHL. (Phase II)

SECONDARY OBJECTIVES: I. To evaluate the progression-free survival of subjects with B-cell NHL receiving maintenance therapy with lenalidomide and rituximab after ASCT. II. To examine whether potential effects of lenalidomide and rituximab on progression-free survival after ASCT, compared with historical controls, vary according to histologic subtype of B-cell NHL. III. To correlate potential associations between peripheral blood levels of lymphocyte subsets including NK, T, and B cells and progression-free survival after ASCT in enrolled subjects. IV. To evaluate potential associations between progression-free survival after ASCT and polymorphisms at position 158 of FCgammaRIIIa receptor in enrolled subjects.

OUTLINE: Patients receive oral lenalidomide once daily on days 1-21of all courses and rituximab IV on day 1of courses 1, 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 2 years.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
      • Cleveland, Ohio, United States, 44111
        • Fairview Cancer Hospital
      • Mayfield Heights, Ohio, United States, 44124
        • Hillcrest Hospital Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form
  • Able to adhere to the study visit schedule and other protocol requirements
  • Histologic diagnosis of CD20+ B-cell NHL including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and other B-cell lymphomas excluding chronic lymphocytic leukemia
  • Received high-dose chemotherapy with autologous stem cell transplantation (ASCT) from 42 to 128 days before enrollment with stable disease, partial response or complete response following ASCT
  • All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study
  • ECOG performance status of =< 2 at study entry; Karnofsky performance status of >= 70% at study entry
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 75,000/mm^3
  • Serum creatinine =< 2.0 mg/dL
  • Phase I subjects must have estimated or measured creatinine clearance >= 60 ml/min
  • Phase II subjects must have estimated or measured creatinine clearance >= 30 ml/min
  • Total bilirubin =< 1.5 mg/dL
  • AST (SGOT) and ALT (SGPT) =< 2 x ULN or =< 5 x ULN if hepatic metastases are present
  • Disease free of prior malignancies for >= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide for cycle 1 (prescriptions must be filled within 7 days)
  • Must also either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide
  • FCBP must also agree to ongoing pregnancy testing
  • Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (subjects intolerant to ASA may use warfarin or low molecular weight heparin)
  • All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that in the opinion of the investigator would prevent the subject from providing written informed consent
  • Pregnant or breast feeding females (lactating females must agree not to breast feed while taking lenalidomide)
  • Use of any other experimental drug or therapy within 28 days of baseline
  • Known hypersensitivity to thalidomide
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Known hypersensitivity to rituximab
  • Concurrent use of other anti-cancer agents or treatments
  • Known positive for HIV or infectious hepatitis, type B or C
  • Residual grade 3 or grade 4 non-hematologic toxicity after ASCT
  • Transfusion requirement (red blood cells or platelets) within 14 days prior to baseline
  • Use of hematopoietic growth factor (including filgrastim, pegfilgrastim, sargramostim, erythropoietin, or darbepoetin) within 14 days prior to baseline
  • Any other condition not defined above, including the presence of laboratory abnormalities, which in the opinion of the investigator would place the subject at unacceptable risk if he/she were to participate in the study, or would confound the ability to interpret data from the study
  • Prior use of lenalidomide either concurrently with rituximab or within 8 weeks following a dose of rituximab
  • Concomitant use of other anti-cancer therapies, including radiation, thalidomide, or other investigational agents is not permitted while subjects are receiving protocol therapy during the treatment phase of the study
  • Corticosteroid therapy also is not permitted while subjects are receiving protocol therapy during the treatment phase of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm I
Patients receive oral lenalidomide once daily on days 1-21 and rituximab IV on day 1of courses 1, 3, 5, 7, 9, and 11.
Biological: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • C2B8 Monoclonal Antibody
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Other: laboratory biomarker analysis
Correlative study
Drug: lenalidomide
Given orally
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Other: flow cytometry
Correlative study
Genetic: polymerase chain reaction
Correlative study
Other Names:
  • PCR
Genetic: nucleic acid sequencing
Correlative study
Other Names:
  • Gene Sequencing
  • Molecular Biology, Nucleic Acid Sequencing
Genetic: polymorphism analysis
Correlative study

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose of lenalidomide (Phase I)
Time Frame: 24 months
24 months
Proportion of subjects who are able to complete 12 cycles of maintenance therapy with lenalidomide and rituximab after autologous stem cell transplantation (ASCT)(PHASE II)
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival after ASCT
Time Frame: 24 months
24 months
Evaluation of potential differences in effects of lenalidomide and rituximab on progression-free survival after ASCT according to histologic subtypes of B-cell NHL
Time Frame: 24 months
24 months
Overall response rate associated with treatment with lenalidomide and rituximab after ASCT, defined as the proportion of subjects with measurable disease at enrollment who achieve a partial response or complete response
Time Frame: 6-12 months
6-12 months
Enumeration of peripheral blood lymphocyte subsets by flow cytometry, including T cells, B cells, and NK cells and analysis of potential associations between these levels with progression-free survival
Time Frame: At study entry, 1 month, and 1 year
At study entry, 1 month, and 1 year
Analysis of FCgammaRIIIa receptor sequences in enrolled subjects to determine the presence or absence of FCgammaRIIIa-158 polymorphisms (V/V, V/F, and F/F); determining potential associations of these polymorphisms with progression-free survival
Time Frame: 12 months
12 months
Incidence of non-relapse mortality (NRM) defined as death from any cause other than B-cell NHL
Time Frame: At 6 and 12 months
At 6 and 12 months
Incidence of unacceptable toxicity during study treatment
Time Frame: At 6 and 12 months
At 6 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Case Comprehensive Cancer Center

Investigators

  • Principal Investigator: Robert Dean, MD, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (ACTUAL)

March 1, 2011

Study Completion (ACTUAL)

March 1, 2012

Study Registration Dates

First Submitted

January 8, 2010

First Submitted That Met QC Criteria

January 8, 2010

First Posted (ESTIMATE)

January 11, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

November 26, 2015

Last Update Submitted That Met QC Criteria

November 25, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CASE2409 (OTHER: Case Comprehensive Cancer Center)
  • NCI-2009-01580 (OTHER: NCI/CTRP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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