A Phase II Study of Lenalidomide (REVLIMID®) in Combination With Rituximab for Patients With CD5+/CD20+ Hematologic Malignancies Who Relapse or Progress After Rituximab
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine response rate for; evaluate safety and tolerability of combination of Rituximab and lenalidomide for treating patients with CD5+/CD20+ CLL or MCL
Dependent upon results
Javier Pinilla, M.D., PhD.
H. Lee Moffitt Cancer Center and Research Institute
United States: Institutional Review Board
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Center for Cancer Care & Research/Watson||Lakeland, Florida 33805|