RATIONALE: Drugs used in chemotherapy, such as pentostatin, cyclophosphamide, and CAMPATH-1H work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well pentostatin, cyclophosphamide, rituximab, and CAMPATH-1H work in treating patients with relapsed or refractory B-cell chronic lymphocytic leukemia.
OBJECTIVES: Primary * Determine the objective response rate (complete remission, partial remission \[PR\], or nodular PR) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (CLL) treated with pentostatin, cyclophosphamide, and rituximab (PCR) followed by CAMPATH-1H . * Determine the presence of minimal residual disease in patients treated with this regimen who achieve a CR or nPR Secondary * Determine the toxicity of this regimen in these patients. * Determine the overall and progression-free survival of patients treated with this regimen. * Evaluate the number of patients who after PCR (or during PCR for PD), only achieve a PR, SD, or PD and who subsequently convert to a higher response category after CAMPATH-1H . Exploratory * Assess the angiogenic profile (i.e., secretion levels of pro- versus anti-angiogenic molecules) of CLL B cell clones as well as bone marrow angiogenesis (i.e., vascular density by immunohistochemistry) at baseline, after PCR, after CAMPATH-1H, every six months (serum only), and at time of response assessment (marrow). * Determine the V\_H gene mutation status and CD38 expression of the B-CLL clones at study entry and at the end of the therapy and assess the association between the VH gene mutation status and CD38 expression and clinical outcome. * Determine surface phenotype (by flow cytometry) and genetic defects (by CLL FISH panel) information on CLL-B cell clones and associate with clinical outcome. * Monitor the T-cell status by repertoire and flow cytometry analysis to determine the nature and extent of T-cell deficiency induced by the PCR and CAMPATH-1H treatment and assess any association with clinical outcome and toxicities.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
102
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States
Aurora Presbyterian Hospital
Aurora, Colorado, United States
Boulder Community Hospital
Boulder, Colorado, United States
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado, United States
St. Anthony Central Hospital
Denver, Colorado, United States
Response Rate
Percent with response (CR, nPR, PR) with two-stage 90% confidence interval
Time frame: 8 weeks after Cycle 6
Molecular Complete Remission (MCR) Rate
Percent of patients who have MCR (clinical CR with flow negative and RT-PCR negative)
Time frame: 3 months post alemtuzumab
Overall Survival (OS)
OS is defined as the time from registration until death from any cause.
Time frame: Up to 5 years from registration
Progression-free Survival (PFS)
PFS is defined as the time from registration until induction failure, institution of non-protocol therapy, relapse or death from any cause in the absence of relapse.
Time frame: Up to 5 years from registration
Number of Patients Who After PCR (or During PCR for PD), Only Achieve a PR, SD, or PD and Who Subsequently Convert to a Higher Response Category After Campath-1H
Time frame: From re-registration up to 5 years (followed for response until progression)
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