A Phase 1 and 2 Trial of Rubidazone in Patients with Acute Leukemia

Thirty-nine previously treated adults with acute leukemia received Rubidazone in a Phase 1 and 2 clinical trial. Thirteen (33%) achieved complete remission, 11 after a single course. Optimal results were obtained after single doses of 450 mg/sq m, from which 8 of 13 (62%) achieved complete remission. Of 19 patients treated with “low” doses (≤450 mg/sq m), 10 (53%) achieved complete remission including 4 of 7 over the age of 50. Higher doses were significantly more toxic and less effective. Neither age, sex, diagnosis, degree of prior therapy, nor previous chemotherapy with an anthracycline antibiotic affected the response rate. Eleven of the 13 complete responders achieved remission after a single course of chemotherapy; median time to complete remission was 29 days. The median duration of remission was 3 months, and the median survival of complete responders was 8 months. Toxic manifestations were similar to those seen with other anthracycline antibiotics, although drug-related deaths during induction at our Phase 2 doses, 1 of 19 (5%), were significantly less frequent than reported after daunorubicin. Maintenance doses of Rubidazone (median, 200 mg/sq m) caused severe granulocytopenia (median, 420/μl) and thrombocytopenia (median, 67,000/μl), which suggests an appropriate dose of 150 to 200 mg/sqm for solid tumor patients, considerably less than the low doses recommended for induction therapy in leukemia. Fatal anthracycline cardiomyopathy occurred after cumulative Rubidazone doses of 1700 to 2600 mg/sqm in 3 patients previously treated with 135- to 270-mg/sqm doses of other anthracyclines. Rubidazone is the most active antileukemic agent that we have tested and deserves further trial in primary combination chemotherapy of patients with acute leukemia as well as systemic investigation in patients with solid tumors.