Clofarabine (CLO) Is Active in Patients (pts) with Refractory and/or Relapsed Non-Hodgkin’s Lymphoma (NHL): A Phase I/II Study.

There is no known standard of care for pts with relapsed and/or refractory NHL who cannot undergo stem cell transplantation (SCT) or have relapsed after SCT. Such pts are candidates for new therapies. CLO is a novel nucleoside analogue with known activity in acute leukemia and myelodysplasia. Previous clinical trials with CLO have established safety and potential activity in a variety of tumors. We performed a phase I/II study of CLO in a heavily pretreated pt population with refractory and/or relapsed NHL regardless of cell type, histology, or grade. Eligible pts were adults over 18 years of age who have relapsed and/or refractory NHL with measurable disease. Pts were required to have adequate performance status, bone marrow function (unless cytopenias were related to disease involvement), renal, cardiac, and liver functions. Pts with bulky disease (>10 cm at any site), known HIV, or immune-related cytopenias were excluded. CLO was given as a 1-hour intravenous infusion for 5 consecutive days every 28 days for a maximum of 6-cycles. All enrolled pts received anti-viral and anti-pneumocystis carinii prophylaxis. Growth factors were administered at the investigator’s discretion. Pts were divided into cohorts of 3 each. CLO was given at 4 mg/m² to the first cohort with escalated doses by 2 mg/m² increments for each cohort. Once the dose-limiting toxicity (DLT) was reached, the phase II portion of this study was initiated at the dose below the DLT level. All pts were followed until disease progression. To date, 13 pts have been enrolled with 7 on the phase I portion and 6 on the phase II portion. For the phase I portion, the median age was 79 (range: 27–81); the median number of prior therapies was 5 (range: 2–6) with 3 pts having relapsed after prior SCT. The median number of given CLO cycles in the phase I portion was 2 (range: 1–5). The DLT at 6 mg/m² was thrombocytpenia establishing 4 mg/m² as the appropriate dose for phase II. For the phase II portion, the median age was 78 (range: 50–83), median number of prior therapies was 2 (range: 1–8). Taken all together (phase I and II pts), 9 out of 13 pts are evaluable for response. (All received at least 1 cycle). There was 1 complete response (CR) and 4 partial responses (PR) for an overall response rate (OR) of 55%. Four patients demonstrated stable disease (SD) with one of them progressing shortly after 2 months. Eight patients remain alive (overall survival: 61%) at a median follow up of 4 months (range: 1–13). Median times to progression and duration of response have not been reached in responding pts.

View large

View Large

CLO is active in heavily pretreated refractory and/or relapsed NHL. The drug has an acceptable toxicity profile. Myelosuppresion is the major adverse event in this heavily pretreated population. The study continues to accrue patients and will be updated at the meeting.