The phase 1 dose escalation involved cohorts of 6-12 patients who were assigned to receive mitoxantrone dose levels of 12, 14, 16, or 18 mg/m2 per day on days 1-3. The doses of the remaining drugs in the combination were fixed at 300 mcg or 480 mcg of G-CSF on days 0-5, 5 mg/m2 of cladribine on days 1-5, and 2 mg/m2 of cytarabine on days 1-5.
“All patients received GCLAM induction at their assigned mitoxantrone dose level. If CR wasn’t achieved with cycle 1, a second identical course of GCLAM was given,” Dr. Halpern explained, noting that patients with resistant disease after 2 cycles were taken off the study.
If CR or CRi was achieved within 1-2 cycles of induction, up to 4 cycles of consolidation with G-CLA (mitoxantrone omitted) were allowed, and responders could proceed with transplant at any time.
In phase 2, patients received the maximum tolerated dose of mitoxantrone (16mg/m2 per day), as defined in phase 1.
“Relapsed and refractory AML and high grade myeloid neoplasms are a challenging disease to treat. With an overall response rate of 60%, this regimen showed efficacy in a heavily pretreated patient population,” Dr. Halpern said. “And many of the responders were able to go on to receive a stem cell transplant, the only known curative option in this situation.”
A follow-up study is currently exploring the relative value of decitabine priming followed by GCLAM in this setting, she said.
Dr. Halpern reported having no relevant financial disclosures.
sworcester@frontlinemedcom.com
SOURCE: Halpern AB et al. ASH 2017, Abstract 149