Phase IB/II of CPX-351 as Maintenance Therapy in AML Patients Ineligible for Bone Marrow Transplantation
This is a phase IB/II study with a 3+3 dose de-escalation study design. Patients will continue maintenance treatment with CPX-351 for 6 cycles on D1 and D3, as long as patient remains in CR. The dose de-escalation will be one dose given on D1 only, every 28 days pending toxicity. The maximum tolerated dose will be used for the phase II expansion portion of the study.
• Newly diagnosed patients \> 18 years of age
• Patients must be in CR or CRh (complete remission with partial count recovery).
• Must have received ANY induction treatment with standard consolidation or hypomethylating agent (HMA) + venetoclax, for up to 6 cycles or no more than one year of treatment.
• Must be able to start therapy within 3 months of last documented CR
• De novo or secondary AML/treatment related AML (non-M3) including AML with myelodysplasia-related changes (MRC), histologically confirmed
• Patients must be ineligible for allogeneic BMT (for any reason including poor performance status, patient's preference, favorable AML not a candidate for transplant, or comorbidities and age precluding from transplant etc)
• Cardiac ejection fraction ≥ 50% by transthoracic echocardiography or MUGA scan
• Adequate hepatic and renal function defined as:
‣ Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN)
⁃ Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 is permissible if due to disease.
⁃ Bilirubin ≤3 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
⁃ Estimated Creatinine Clearance ≥30 ml/min (Cockcroft-Gault based on actual weight) (See Appendix A)
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3 (Appendix A)
• Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.
• Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices \[IUDs\], sexual abstinence, or sterilized partner) during the period of therapy and for at least 6 months after the last dose of study drug