Clinical trial NCT00609869
Conditions: Lymphocytic Leukemia Mantle Cell Lymphoma
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Start date: 2007-10-01; Completion date: 2015-08-01
Enrollment: 29 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed 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.

Arms: arm 1: 28 day cycles of Lenalidomide administered orally and Rituximab administered intravenously.

Lenalidomide: Escalating doses starting with of 2.5 mg daily on 28-days cycles.

Rituximab: at 375 mg/m\^2 on a weekly basis for the first cycle starting on day 15.
Interventions: intervention 1: Lenalidomide intervention 2: Rituximab
Intervention descriptions: intervention 1: Lenalidomide was administered orally with escalating doses on 28-days cycles. The first cycle was administered with a starting dose of 2.5 mg daily on days 1-7, 5mg on days 8-14 and 10 mg on days 15-21, followed by seven days off. On cycle 2 and beyond lenalidomide was administered at 20 mg daily on days 1-21. intervention 2: Rituximab was administered at 375 mg/m\^2 intravenously on a weekly basis for the first cycle starting on day 15. Subsequent rituximab doses were administered on day one of cycle 2 and beyond, every 4 weeks. Doses were repeated on 28-day cycles until disease progression or unacceptable toxicity, but were planned for 12 cycles.

Protocol documents: