Clinical Trials:
The efficacy of omacetaxine mepesuccinate was eva luated using a combined cohort of adult patients with CML from two trials. The combined cohort consisted of patients who had received 2 or more approved TKIs and had, at a minimum, documented evidence of resistance or intolerance to dasatinib and/or nilotinib. ­Patients were treated with omacetaxine mepesuccinate at a dose of 1.25mg/m2 administered subcutaneously twice daily for 14 consecutive days every 28 days (induction cycle). Responding patients were then treated with the same dose and twice daily schedule for 7 consecutive days every 28 days (maintenance cycle). Patients were allowed to continue to receive maintenance treatment for up to 24 months.

In the first trial, a total of 76 patients with chronic phase CML were included in the efficacy analysis. Thirty-six (47%) patients had failed treatment with imatinib, dasatinib, and nilotinib. Most patients had also received prior non-TKI treatments, most commonly hydroxyurea (54%), interferon (30%), and/or cytarabine (29%). At efficacy endpoint, 18% (14/76) achieved a major cytogenetic response (MCyR) with a mean time to MCyR onset of 3.5 months. The median ­duration of MCyR for these patients was 12.5 months (Kaplan-Meier estimate).

In the second trial, a total of 35 patients with accelerated phase CML were included in the efficacy analysis. Twenty-two (63%) of 35 patients with accelerated phase had failed treatment with imatinib, dasatinib, and nilotinib. Most patients had also received prior non-TKI treatments, most commonly hydroxyurea (43%), interferon (31%), and/or cytarabine (29%). At efficacy endpoint, 14% (5/35) achieved a major hematologic ­response (MaHR) with a mean time to response onset of 2.3 months. The median duration of MaHR for these patients was 4.7 months (Kaplan-Meier estimate).

Legal Classification:
Rx

Adults:
Induction: 1.25mg/m2 by SC injection twice daily for 14 consecutive days every 28 days, over a 28-day cycle. Repeat cycles every 28 days until hematologic response achieved. Maintenance: 1.25mg/m2 by SC injection twice daily for 7 consecutive days every 28 days, over a 28-day cycle. Dose adjustments and modifications: see full labeling.

Children:
Not established.

Warnings/Precautions:
Risk of myelosuppression (thrombocytopenia, neutropenia, anemia), hemorrhage. Monitor CBCs with platelets weekly during induction, initial maintenance cycles, and every 2 weeks during later cycles. Monitor glucose levels (esp. in diabetics). Avoid in poorly controlled diabetes until glycemic control is ­established. Elderly. Pregnancy (Cat. D); avoid. Nursing mothers: not recommended.

Interaction(s)
Avoid concomitant anticoagulants, aspirin, NSAIDs if platelets <50,000/microliters; may increase risk of bleeding.

Adverse Reaction(s)
Thrombocytopenia, anemia, neutropenia, diarrhea, nausea, fatigue, asthenia, injection site reaction, pyrexia, infection, lymphopenia; bleeding, hyperglycemia.

How Supplied:
Single-use vial—1

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