Phase Ii Study Of Fludarabine, Carboplatin, And Topotecan With Thalidomide (Fctt) For Patients With Relapsed/Refractory Or Secondary Acute Myelogenous Leukemia, Chronic Myeloid Leukemia And Advanced Myelodysplastic Syndromes.

6630 Background: Limited treatment options are available for patients with AML that has relapsed or develops as a result of prior chemotherapy or hematologic disorders. Methods: We designed a phase II study of fludarabine (15mg/m2 x 5 days) given concurrently with carboplatin (AUC 12 by CIVI over 5 days) followed by topotecan (0.85 mg/m2 daily by CIVI over 72 hours) based on promising results of a phase I study. Thalidomide was given at a dose of 100mg daily for 1 week then 200 mg daily for potential anti-angiogenic activity as well as single agent response in myelodysplasia. 35 pts were enrolled with median age 60 years (range 40 to 78). 14 pts had AML secondary to cytotoxic chemotherapy or prior hematologic conditions and had not received prior therapy for acute leukemia (Group 1). 21 pts had relapsed or refractory AML (Group 2). Two patients had failed prior autologous stem cell transplantation. Results: Seven of 14 (50%) pts in Group 1 and 8 of 21 (38%) pts in Group 2 achieved bone marrow aplasia. Four of 14 (29%) pts in Group 1 and 5 of 21 (23%) pts in Group 2 achieved a CR or CR with persistent thrombocytopenia (CRp). Two pts required two cycles of FCTT to achieve remission. In pts who achieved CR or CRp, the median time to ANC > 500/uL was 31 days (range 20 to 48) and time to platelet transfusion independence was 40 days (range 23 to 82). Median remission duration was 153 days. Three pts subsequently underwent allogeneic stem cell transplantation. Six of the 35 pts required modification of the thalidomide dose and 7 of 35 discontinued thalidomide due to grade 3 neutropenic enterocolitis (3 pts), neuropathy (3 pts), thrombotic complications (2 pts), rash (4 pts) and persistent neutropenia (1 pt). There were 5 treatment related deaths. 4 pts died of infectious complications before bone marrow recovery and 1 died of cardiac tamponade. Grade 3 or greater extramedullary toxicity was comparable to other salvage regimens. Conclusion: FCTT appears to be an active, well-tolerated regimen for both untreated high-risk AML as well as relapsed or refractory disease. Combinations of FCTT with other promising biologic agents are planned. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene