Clinical trial NCT00765245: Lenalidomide With or Without Rituximab After Standard Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma
Official title: A Phase II Randomized Study of Lenalidomide or Lenalidomide and Rituximab as Maintenance Therapy Following Standard Chemotherapy for Patients With High/High-intermediate Risk Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: stage I adult diffuse large cell lymphoma
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
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-10-02
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Disease-free Survival at 1 Year
timeFrame: From on-treatment date to disease recurrence, up to 1 year
Secondary outcomes:
measure: Disease-free Survival at 2 Years
timeFrame: From on-treatment date to disease recurrence, up to 2 years
measure: Number of Patients With Each Worst-Grade Toxicity
timeFrame: 30 days after completing treatment, for up to 13 months
Other outcomes:
measure: Investigate Potential Predictive Biomarkers of Clinical Response or Resistance to Lenalidomide
timeFrame: up to two years
measure: Exploratory: Concordance Between IHC for GCB and Non-GCB Subtypes to the Gene Expression Profiles Associated With the Subtypes
timeFrame: up to two years
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center - Cool Springs
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Franklin
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Nishitha Reddy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.