Clinical Trials /

Lenalidomide, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large Cell or Follicular B-Cell Lymphoma

NCT00670358

Description:

RATIONALE: Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. 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. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with rituximab and combination chemotherapy may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of lenalidomide when given together with rituximab and combination chemotherapy and to see how well they work in treating patients with newly diagnosed stage II, stage III, or stage IV diffuse large cell or follicular B-cell lymphoma.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Lenalidomide, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Diffuse Large Cell or Follicular B-Cell Lymphoma
  • Official Title: Phase I/II Study of Lenalidomide (Revlimid), Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R2CHOP) Chemoimmunotherapy in Patients With Newly Diagnosed Diffuse Large Cell and Follicular Grade IIIA/B B Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: MC078E
  • SECONDARY ID: P30CA015083
  • SECONDARY ID: MC078E
  • SECONDARY ID: RV-NHL-PI-0325
  • SECONDARY ID: 07-007992
  • SECONDARY ID: NCI-2009-01196
  • NCT ID: NCT00670358

Conditions

  • Lymphoma

Interventions

DrugSynonymsArms
pegfilgrastim
rituximab
cyclophosphamide
doxorubicin hydrochloride
lenalidomide
prednisone
vincristine sulfate

Purpose

RATIONALE: Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. 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. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with rituximab and combination chemotherapy may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of lenalidomide when given together with rituximab and combination chemotherapy and to see how well they work in treating patients with newly diagnosed stage II, stage III, or stage IV diffuse large cell or follicular B-cell lymphoma.

Detailed Description

      OBJECTIVES:

      Primary

        -  To determine the maximum tolerated dose of lenalidomide when given in combination with
           rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in
           patients with newly diagnosed stage II-IV diffuse large cell or grade 3 follicular
           B-cell lymphoma. (Phase I)

        -  To assess the efficacy of this regimen, in terms of event-free survival and response
           rate, in these patients. (Phase II)

        -  To assess the safety of this regimen in these patients. (Phase II)

      Secondary

        -  To assess the host immune function at baseline and after treatment and correlate these
           parameters with tumor response and event-free survival.

      OUTLINE: This is a multicenter, phase I dose-escalation study of lenalidomide followed by a
      phase II study.

        -  Phase I: Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride
           IV, and vincristine IV on day 1, oral prednisone on days 1-5, and oral lenalidomide on
           days 1-10. Patients also receive pegfilgrastim subcutaneously on day 2. Treatment
           repeats every 21 days for up to 6 courses in the absence of disease progression or
           unacceptable toxicity.

        -  Phase II: Patients receive lenalidomide at the maximum tolerated dose determined in
           phase I and rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine,
           prednisone, and pegfilgrastim as in phase I.

      Blood is collected at baseline, before course 3, and after completion of study treatment for
      translational research studies. Research studies include immune function and cytokine
      analysis, T- and B- quantitative lymphocyte analysis, and single nucleotide polymorphism
      analysis.

      After completion of study therapy, patients are followed every 3 months for 1 year, every 4
      months for 1 year, and then every 6 months for 3 years.
    

Trial Arms

NameTypeDescriptionInterventions

Eligibility Criteria

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed diffuse large cell or grade 3A/B follicular lymphoma

               -  Newly diagnosed disease

               -  Stage II, III, or IV disease

          -  Measurable disease, defined as ≥ 1 lesion ≥ 1.5 cm in one diameter, as detected by CT
             scan or PET-CT scan (PET/CT fusion)

          -  CD20-positive disease

          -  No post-transplant lymphoproliferative disorder (PTLD)

          -  No CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-2

          -  ANC ≥ 1,500/mm³

          -  Platelet count ≥ 100,000/mm³

          -  Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin normal

          -  Alkaline phosphatase ≤ 3 times ULN (5 times ULN if direct liver involvement by
             lymphoma)

          -  AST ≤ 3 times ULN (5 times ULN if direct liver involvement by lymphoma)

          -  Creatinine ≤ 2 times ULN

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile female patients must use effective double-method contraception for ≥ 28 days
             before, during, and for ≥ 28 days after completion of study therapy

          -  Fertile male patients must use effective contraception during and for ≥ 28 days after
             completion of study therapy, even if they have had a successful vasectomy

          -  No blood, sperm, or semen donation during and for ≥ 28 days after completion of study
             therapy

          -  Willing to return to enrolling institution for follow-up

          -  Willing to provide blood samples for translational research purposes

          -  No comorbid systemic illness or other severe concurrent disease that, in the judgment
             of the investigator, would preclude study entry or significantly interfere with the
             proper assessment of safety and toxicity of the prescribed study regimen

          -  No known HIV positivity

          -  Not immunocompromised

          -  No concurrent uncontrolled 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/social situation that would preclude compliance with study
                  requirements

          -  No other active malignancy, except localized nonmelanotic skin cancer or any cancer
             that, in the judgment of the investigator, has been treated with curative intent and
             will not interfere with the study treatment plan and response assessment

          -  No myocardial infarction within the past 6 months

          -  No congestive heart failure requiring ongoing maintenance therapy for life-threatening
             ventricular arrhythmias

          -  Ejection fraction ≥ 45% by MUGA or ECHO

          -  No history of life threatening or recurrent thrombosis/embolism (unless on
             anticoagulation therapy during study treatment)

        PRIOR CONCURRENT THERAPY:

          -  No prior radiotherapy to ≥ 25% of the bone marrow

          -  No concurrent erythroid-stimulating agents (e.g., Procrit, Aranesp)

          -  No other concurrent treatment for lymphoma

          -  No concurrent radiotherapy, chemotherapy, or immunotherapy for another active
             malignancy

          -  Able to receive concurrent prophylactic anticoagulation therapy (e.g., low-dose
             aspirin [81 mg] daily or an alternative prophylaxis [e.g., warfarin or low molecular
             weight heparin])
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Toxicity as assessed by NCI CTCAE v3.0 (Phase I)
Time Frame:
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:
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Description:
Measure:Overall complete response rate
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Description:
Measure:Event-free survival
Time Frame:
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Description:
Measure:Overall survival
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Description:
Measure:Progression-free survival
Time Frame:
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Description:
Measure:Duration of response
Time Frame:
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Description:
Measure:Immune function before and after treatment as assessed by T-, B-, and NK-cell quantification
Time Frame:
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Description:
Measure:Correlation of immune function with clinical outcomes
Time Frame:
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Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

Trial Keywords

  • contiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • contiguous stage II grade 3 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 3 follicular lymphoma

Last Updated

June 19, 2019