Lenalidomide in Comb w/Rituximab for Pts w/CD5+/CD20+ Hem Malignancies Who Relapse/Progress After Rituximab

Mantle Cell Lymphoma Clinical Trial

Official title: A Phase II Study of Lenalidomide (REVLIMID®) in Combination With Rituximab for Patients With CD5+/CD20+ Hematologic Malignancies Who Relapse or Progress After Rituximab

Status Completed

Clinical Trial Summary

The purpose of this research is to evaluate the use of Rituximab in combination with Revlimid in the treatment of refractory Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL). Revlimid® is a drug that changes the immune system and it may also get in the way with the growth of tiny blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. Revlimid® is approved by the Food and Drug Administration (FDA) for the treatment of specific types of Myelodysplasia syndrome (MDS) and Multiple Myeloma, two different types of blood cancer. It is currently being tested in a variety of cancer conditions. In this case it is considered experimental.

Clinical Trial Description

This phase II trial will use a Simon's two stage design enrolling a total of 28 subjects. Ten will be accrued during stage 1 and 18 during stage 2. If 3 or fewer responses (CR+PR) are observed during the first stage then the trial is stopped early. Given that the 'true' response probability is 30%, there is a 64.96% probability of ending the trial during stage

1. However, if the 'true' response probability is 60% then there is a 5.48% probability that the trial will be stopped in stage 1. If more than 3 responses are observed in stage 1, another 18 patients will be accrued in stage 2. If 12 or fewer responses are observed by the end of the trial, then no further investigation of the drug is warranted. Otherwise, conclude that the drug is worthy of further investigation. The alpha level of the design is 0.04 and the power is 0.91.

Patients with confirmed CD5+/CD20+ MCL or CLL who have relapsed or progressed after Rituximab therapy following a minimum of 6 months duration of response (SD, PR, or CR as defined by Appendix D) will be eligible for this study. Baseline evaluation of patients prior to enrollment in this study will include complete blood counts (CBCs), serum chemistries, liver function tests, kidney function tests, lactate dehydrogenase (LDH); and CT scans of the chest, abdomen and pelvis; and bone marrow biopsy. The exact values for the status of organ function allowable on this protocol are included in the body of this document. Bone marrow aspirates, biopsies and standard FISH evaluation for specific cytogenetic abnormalities will be obtained by the clinical site. An adequate bone marrow aspirate sample is required for a subject to be eligible to participate in this study. All assessments will be completed according to Schedule of Study Assessments.

Patients who meet eligibility criteria and have signed the informed consents will have further laboratory evaluation which will involve flow cytometry of the peripheral blood to evaluate: 1) CD20 density on the leukemic cells (CLL patients only), 2) the percentage of CD56+ cells to evaluate the baseline level of natural killer (NK) cell, 3) the density of activation antigens (CD2, CD11a, CD31, CD38, and CD69) on CD56+ cells, and 4) CD38 (ZAP-70) expression. Pretreatment serum baseline values for Interferon-alpha (IFN-alpha), Tumor necrosis factor-alpha (TNF-A), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and soluble IL-2 receptor will be obtained. A baseline CBC, flow cytometry and cytokine studies will be obtained on Day 1 prior to start of Lenalidomide.

All patients will have a full immunological evaluation on Day 15 of Lenalidomide therapy prior to Rituximab administration. A bone marrow biopsy will be performed on all patients (CLL and MCL) with prior documented bone marrow involvement once between Days 13- 15 to assess the impact of the lenalidomide on the malignant cells and the surface density of CD20 for patients with CLL before the administration of Rituximab. Flow cytometry on the aspirate specimen will be performed at Moffitt Cancer Center. The cytokine studies will be drawn on Day 15, prior to the administration of Rituximab. Starting on Day 15 after collection of specimens, the patients will receive four weekly doses of Rituximab (375 mg/m^2) concurrent with lenalidomide as per the cycle schedule. Lenalidomide therapy will be continued until progression of disease, unacceptable toxicity or patient withdrawal.

Patient assessment during the clinical trial will be performed by a physician and will occur prior to the administration of each dose of Rituximab. The evaluation will include CBC, routine chemistries, kidney function, liver function, and LDH. The impact of the treatment on any lymphadenopathy or splenomegaly will be documented. Any toxicities noted during these evaluations will be noted. After the four weekly doses of Rituximab, if the pretreatment bone marrow biopsy was positive, the patient will have a repeat bone marrow biopsy to assess response. If the patient had splenomegaly or lymphadenopathy prior to entry into the trial, the patient will need repeat CT scans to assess response. The scans and bone marrow biopsies should be performed two weeks after the patient's last dose of Rituximab.

Follow-up of patients after completing the Rituximab treatment for patients who have not progressed while on therapy will involve a CBC, routine chemistries, liver function tests, and LDH drawn according to the Schedule of Assessments. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia, Lymphoid
• Lymphocytic Leukemia
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

• NCT number: NCT00609869
• Study type: Interventional
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Status: Completed
• Phase: Phase 2
• Start date: October 2007
• Completion date: August 2015