A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated, Stage II, III or IV CLL.

The decision to treat indolent CLL is often based on progressive bulky disease, worsening symptoms, and increasing hematological derangement. When treatment is indicated, these lymphoproliferative disorders are sensitive to combination immunochemotherapies utilizing pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody. P+C+R represents a promising new approach in the treatment of patients with CLL. Eligibility criteria allow both treated and treatment-naïve patients diagnosed with Stage II/III/IV CLL (modified Rai classification) to be enrolled. Treatment consisted of intravenous infusions of P (4 mg/m²), C (600 mg/m²), and R (375 mg/m²) on day 1 of a 21-day cycle for a total of up to 10 cycles. Clinical evaluation (including CT scan) was performed after cycles 2, 4, 6, 8 and 10 (if necessary). The intent-to-treat (ITT) population consisted of 70 CLL patients (median age 64, range 35–83) who received a total of 286 cycles (median 4.5 per patient). ECOG status at enrollment was 0 (68%), 1 (28%) and 2 (4%). The overall response rate (CR+Cru+PR) of the 50 evaluable patients was 52% (CR 8%, Cru 14%, PR 30%, SD 46% and PD or RD 2%). 2 grade 4 neutropenia and 1 grade 4 respiratory distress was documented. 4 deaths have been recorded, all in elderly patients (>80 years old), due to acute respiratory failure, myocardial infarction, pulmonary edema and sepsis. This immunochemotherapeutic regimen is active in Stage II/III/IV CLL and the incidence of significant toxicities was low with deaths occurring only in elderly (>80 years old) patients. The study results will be updated at the meeting.