Background: Forodesine, a potent, rationally designed purine nucleoside phosphorylase inhibitor, has shown clinical activity in T-cell leukemia following IV administration. This phase II study was undertaken to evaluate further the efficacy and safety of IV forodesine in patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL).

Methods: In this open-label, single-arm, multicenter, ongoing study, patients received forodesine, 40 mg/m2 IV, 5 days each week (1 cycle) for a total of 6 cycles. The dose was escalated to 90 mg/m2 in patients who were not responding after cycle 2. The primary end point was objective response (OR), which included complete response (CR), CR with incomplete recovery of peripheral blood cell counts (CRi), and partial response (PR).

Results: In total, 34 T-ALL patients (median age, 31 yr; range, 3–76 yr) with relapsed/refractory T-ALL (median, 3 prior treatments) received forodesine IV. The OR rate was 32.4% (11 patients; 7 [20.6%] CR, 0 CRi [0%] and 4 [11.8%] PR). Patient demographics and response for the 7 CR patients are shown in the Table. One CR patient has continued to receive treatment for almost 1 year. Two patients with CR proceeded to hematopoietic stem cell transplantation following remission. The restoration of normal hematopoiesis observed in patients while receiving therapy indicates a specificity of forodesine for leukemic cell populations. A total of 18 patients were dose escalated to 90 mg/m2 of forodesine after cycle 2 due to a lack of response. None of these patients demonstrated an improved response with dose escalation. The most frequently reported possibly drug-related AEs without regard to grade were nausea (22%), headache (16%), thrombocytopenia (14%), leukopenia (14%), asthenia (14%), and anemia (11%). Possibly drug-related AEs of grade 3 and higher occurring in ≥2 patients were thrombocytopenia (3 patients; 8%) and leukopenia and lymphopenia (2 patients each; 5%).

Conclusions: IV forodesine is effective as a single agent in the treatment of patients with relapsed or refractory T-ALL and is safe and well tolerated. Additionally, 40 mg/m2 has been confirmed as the dose for subsequent phase II development in T-ALL.

T-ALL Patients With Complete Response

Patient No.No. of Previous TreatmentsAge/GenderRelapsed/RefractoryWeeks of TxTime to CRTime to Progression(Days)Overall Survival (Days)
#Patient died in CR due to a cardiovascular event *Patient discontinued treatment and then progressed †Patient underwent transplantation following remission 
1# 23/M Relapsed 2 weeks 77 77 
60/M Relapsed 31 6 weeks 238 238+ 
3* 28/F Relapsed 10 2 weeks 119 459+ 
3/F Relapsed 51 2 weeks 398+ 398+ 
5† 20/F Refractory 6 weeks 207 224 
76/M Refractory 12 2 weeks 91 91+ 
7† 27/M Refractory 2 weeks 180+ 180+ 
Patient No.No. of Previous TreatmentsAge/GenderRelapsed/RefractoryWeeks of TxTime to CRTime to Progression(Days)Overall Survival (Days)
#Patient died in CR due to a cardiovascular event *Patient discontinued treatment and then progressed †Patient underwent transplantation following remission 
1# 23/M Relapsed 2 weeks 77 77 
60/M Relapsed 31 6 weeks 238 238+ 
3* 28/F Relapsed 10 2 weeks 119 459+ 
3/F Relapsed 51 2 weeks 398+ 398+ 
5† 20/F Refractory 6 weeks 207 224 
76/M Refractory 12 2 weeks 91 91+ 
7† 27/M Refractory 2 weeks 180+ 180+ 

Disclosures: Consultant for BioCryst Pharmaceuticals, Inc.; Member of BioCryst Pharmaceuticals, Inc advisory board.

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