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

Sponsor

Mayo Clinic (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00670358

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

172.2

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

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

Actual Study Start Date :

Aug 25, 2008

Actual Primary Completion Date :

May 7, 2021

Anticipated Study Completion Date :

Dec 31, 2022

Outcome Measures

Primary Outcome Measures

Toxicity as assessed by NCI CTCAE v3.0 (Phase I) []
Event-free survival at 12 months (Phase II) []

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259-5499
2	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224
3	Mayo Clinic	Rochester	Minnesota	United States	55905