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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

Primary Purpose

Lymphoma

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

pegfilgrastim

rituximab

cyclophosphamide

doxorubicin hydrochloride

lenalidomide

prednisone

vincristine sulfate

polymorphism analysis

laboratory biomarker analysis

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept 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])

Sites / Locations

Mayo Clinic in Arizona
Mayo Clinic in Florida
Mayo Clinic

Outcomes

Primary Outcome Measures

Toxicity as Assessed by NCI CTCAE v3.0 (Phase I)

Event-free > Survival at 12 Months (Phase 2, DLBCL/Mixed Dose Level 3)

Other Phase II Cohorts were not evaluable for event-free survival analysis.

Progression-free > Survival at 24 Months (Phase 2, Transformed/Composite)

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions Other Phase II Cohorts were not evaluable for progression-free survival analysis.

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

Full Information

NCT ID

NCT00670358

First Posted

April 30, 2008

Last Updated

August 17, 2023

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00670358

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 25, 2008 (Actual)

Primary Completion Date

May 7, 2021 (Actual)

Study Completion Date

November 11, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

138 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

pegfilgrastim

Intervention Type

Biological

Intervention Name(s)

rituximab

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Intervention Type

Drug

Intervention Name(s)

doxorubicin hydrochloride

Intervention Type

Drug

Intervention Name(s)

lenalidomide

Intervention Type

Drug

Intervention Name(s)

prednisone

Intervention Type

Drug

Intervention Name(s)

vincristine sulfate

Intervention Type

Genetic

Intervention Name(s)

polymorphism analysis

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Primary Outcome Measure Information:

Title

Toxicity as Assessed by NCI CTCAE v3.0 (Phase I)

Time Frame

5 years

Title

Event-free > Survival at 12 Months (Phase 2, DLBCL/Mixed Dose Level 3)

Description

Other Phase II Cohorts were not evaluable for event-free survival analysis.

Time Frame

1 year

Title

Progression-free > Survival at 24 Months (Phase 2, Transformed/Composite)

Description

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Overall Response Rate

Time Frame

When all patients either have a CR or have completed observation.

Title

Overall Complete Response Rate

Time Frame

When all patients either have a CR or have completed observation.

Title

Event-free Survival

Time Frame

5 years

Title

Overall Survival

Time Frame

5 years

Title

Progression-free Survival

Time Frame

5 years

Title

Duration of Response

Time Frame

5 years

Title

Immune Function Before and After Treatment as Assessed by T-, B-, and NK-cell Quantification

Time Frame

5 years

Title

Correlation of Immune Function With Clinical Outcomes

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

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])

Overall Study Officials: