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

This study is currently recruiting participants.
Verified March 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00670358
First received: April 30, 2008
Last updated: March 6, 2014
Last verified: March 2014
  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.


Condition Intervention Phase
Lymphoma
Biological: pegfilgrastim
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: lenalidomide
Drug: prednisone
Drug: vincristine sulfate
Genetic: polymorphism analysis
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Toxicity as assessed by NCI CTCAE v3.0 (Phase I) [ Designated as safety issue: Yes ]
  • Event-free survival at 12 months (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate [ Designated as safety issue: No ]
  • Overall complete response rate [ Designated as safety issue: No ]
  • Event-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Immune function before and after treatment as assessed by T-, B-, and NK-cell quantification [ Designated as safety issue: No ]
  • Correlation of immune function with clinical outcomes [ Designated as safety issue: No ]

Estimated Enrollment: 47
Study Start Date: August 2008
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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])
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00670358

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259-5499
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Craig B. Reeder, M.D.         
United States, Florida
Mayo Clinic in Florida Active, not recruiting
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Office    507-538-7623      
Principal Investigator: Grzegorz S. Nowakowski, M.D.         
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Grzegorz S. Nowakowski, M.D. Mayo Clinic
Principal Investigator: Craig B. Reeder, M.D. Mayo Clinic in Arizona
Principal Investigator: Candido E. Rivera, M.D. Mayo Clinic in Florida
Study Chair: Judy Olmos, R.N. Mayo Clinic in Florida
Study Chair: Michele Maharaj, R.N. Mayo Clinic in Florida
  More Information

Additional Information:
No publications provided

Responsible Party: Grzegorz S. Nowakowski, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00670358     History of Changes
Other Study ID Numbers: MC078E, P30CA015083, MC078E, RV-NHL-PI-0325, 07-007992, NCI-2009-01196
Study First Received: April 30, 2008
Last Updated: March 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Thalidomide
Rituximab
Lenalidomide
Doxorubicin
Prednisone
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on April 16, 2014