Lenalidomide With or Without Rituximab After Standard Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma

NCT ID: NCT00765245

Last Updated: 2016-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2014-11-30

Brief Summary

RATIONALE: Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. It may also 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. It is not yet known whether lenalidomide is more effective with or without rituximab in treating diffuse large B-cell non-Hodgkin lymphoma.

PURPOSE: This randomized phase II trial is studying lenalidomide to see how well it works when given with or without rituximab after standard chemotherapy in treating patients with diffuse large B-cell non-Hodgkin lymphoma.

Detailed Description

OBJECTIVES:

Primary

• To assess the 1-year disease-free and relapse-free survival of patients with high- or high/intermediate-risk diffuse large B-cell non-Hodgkin lymphoma treated with maintenance therapy comprising lenalidomide with or without rituximab following standard chemotherapy.

Secondary

• To assess the 2-year disease-free survival of patients treated with these regimens.
• To define the safety and toxicity profile of these regimens.
• To perform antibody-dependent cellular cytotoxicity assays using peripheral blood mononuclear cell samples from these patients.
• To assess the change in the number of natural killer cells by flow cytometric analysis.
• To evaluate cytokines including, but not limited to, sIL-2R, IL-6, IL-15, IL-12, TNF-α, and IFN-γ in these patients.
• To study the KIR genotype receptor and FCγR polymorphisms.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity.

Peripheral blood mononuclear cells are collected periodically for correlative studies. Samples are analyzed for change in the number of natural killer cells by flow cytometry; antibody-dependent cellular cytotoxicity by assay; cytokines; KIR genotype receptor; and FCγR polymorphisms.

After completion of study therapy, patients are followed at 30 days and then every 3 months for 1 year.

Conditions

Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I: Lenalidomide

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Arm II: Lenalidomide and Rituximab IV

Patients receive lenalidomide as in arm I and rituximab IV on day 8 of courses 1, 3, 5, 7, 9, and 11 in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles

Rituximab

Intervention Type: DRUG

Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.

Interventions

Lenalidomide

Orally once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Intervention Type: DRUG

Lenalidomide

Lenalidomide 20 mg daily, Days 1-21, followed by 7 days rest (28-day cycle). Cycles will be repeated every 28 days for a total of 12 cycles

Intervention Type: DRUG

Rituximab

Rituximab 375 mg/m2 intravenously (IV) starting on Day 8, Cycle 1 of lenalidomide. Rituximab will be repeated on Day 8 of odd numbered cycles (Cycles 1, 3, 5, 7, 9, and 11) for a total of 6 doses from randomization.

Intervention Type: DRUG

Other Intervention Names

Revlimid; Revlimid; Rituxan

Eligibility Criteria

Inclusion Criteria

1. Understand and voluntarily sign an Informed Consent form

2. Age > 18 years at time of signing the Informed Consent Form

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Patients with histological confirmation of diffuse large B cell lymphoma with at least one of the following characteristics:

• High or intermediate IPI score (See Appendix 8.0 for IPI scoring criteria)
• Patients who are still PET scan positive mid therapy with R-CHOP, but, have turned negative after completion of therapy.
• Low risk International prognostic index ie., an IPI score of <3 if age >60 years or <2 if age is less than or equal to 60 with c-myc positive by Fluorescent In situ Hybridization.

5. No other previous lymphoma therapy, hormonal therapy or surgery, except for standard therapy with R-CHOP with or without radiation and with or without prophylactic Methotrexate therapy. Patients must be enrolled within 4-12 weeks of completion of therapy.

6. At the time of study entry following standard therapy with R-CHOP±RT, patients should be in complete remission.

7. ECOG performance status of ≤ 2 at study entry

8. Laboratory test results within these ranges:

• Absolute neutrophil count ≥ 1500/mm³
• Platelet count ≥100K /mm³
• Serum creatinine ≤ 2.0 mg/dL
• Total bilirubin ≤ 1.5 mg/dL
• AST (SGOT) and ALT (SGPT) ≤ 2 x ULN

9. Disease free of prior malignancies for ≥ 3 years with exception of currently treated basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.

10. All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the Revlimid REMS® program.

•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 and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by the Revlimid REMS® program) and must 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.

11. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation, if patients are thought to be at an elevated risk of thrombosis.

Exclusion Criteria

1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the Informed Consent

2. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).

3. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

4. Use of any other experimental drug or therapy within 28 days of baseline.

5. Known hypersensitivity to thalidomide.

6. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

7. Any prior use of lenalidomide.

8. Concurrent use of other anti-cancer agents or treatments.

9. Known positive for HIV or infectious hepatitis, type B or C.

10. A diagnosis of deep vein thromboses in the preceding 3 months of study enrollment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Nishitha Reddy, MD

Assistant Professor of Medicine; Hematologist/Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nishitha Reddy, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center

Locations

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center at Franklin

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

References

Vose JM, Habermann TM, Czuczman MS, Zinzani PL, Reeder CB, Tuscano JM, Lossos IS, Li J, Pietronigro D, Witzig TE. Single-agent lenalidomide is active in patients with relapsed or refractory aggressive non-Hodgkin lymphoma who received prior stem cell transplantation. Br J Haematol. 2013 Sep;162(5):639-47. doi: 10.1111/bjh.12449. Epub 2013 Jul 9.

Reference Type: DERIVED

PMID: 23834234 (View on PubMed)

Related Links

http://www.vicc.org/ct/

Vanderbilt-Ingram Cancer Center, Find a Clinical Trial

Other Identifiers

P30CA068485

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VICC HEM 0835

Identifier Type: -

Identifier Source: org_study_id