Trial of CPX-351 in Adult Patients With First Relapse Acute Myeloid Leukemia (AML)

Phase IIB, Multicenter, Randomized, Open-Label Trial Of CPX-351 (Cytarabine : Daunorubicin) Liposome Injection Versus Intensive Salvage Therapy In Adult Patients ≤ 65 Years Old With AML In First Relapse Following An Initial CR > 1 Month Duration

The study investigates if CPX-351 will be a) more effective than the standard intensive salvage AML treatment and b) more tolerable than the standard intensive salvage treatment regimens.

The study compares the investigational product CPX-351 vs the standard intensive salvage treatment for first relapse AML patients.

This study is a randomized, open-label, parallel-arm, fixed-dose, standard therapy controlled Phase IIB trial. Study enrollment duration is expected to be approximately 12-18 months. On entry, patients are randomized to receive either CPX-351 or intensive first salvage treatment.

Patients are stratified to balance the likelihood of obtaining a CR and the duration of CR between the two arms.

Inclusion Criteria:

• Ability to understand and voluntarily sign an informed consent form

• Age ≥18 and ≤65 years at the time of relapse

• Pathological confirmation of relapsed AML after initial CR of >1 month duration

• Eastern Cooperative Oncology Group (ECOG) performance status 0- 2

• Able to adhere to the study visit schedule and other protocol requirements

• Laboratory values fulfilling the following:

  • Serum creatinine < 2.0 mg/dL
  • Serum total bilirubin < 2.0 mg/dL
  • Serum alanine aminotransferase or aspartate aminotransferase <3xULN Note: If elevated liver enzymes are related to disease; contact medical monitor to discuss.

• Cardiac ejection fraction > 50% by echocardiography or MUGA scan

• All men and women must agree to practice effective contraception during the study period and for 3 months afterward if not otherwise documented to be infertile.

Exclusion Criteria:

• Patients with active second malignancies are excluded. Patients with second malignancies in remission may be eligible if there is no clinical evidence of active disease, documented by imaging, with tumor marker studies, etc., at screening. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are eligible. In all cases, the second malignancy and its non-chemotherapy treatment must not interfere with the investigators ability to assess the safety or efficacy of the study treatment
• Patients with acute promyelocytic leukemia [t(15;17)]
• Total lifetime anthracycline exposure exceeding the equivalent of 368 mg/m2 of daunorubicin (or equivalent) prior to start of study therapy
• Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent
• Administration of any antineoplastic therapy within 4 weeks of therapy; intended to treat first relapse. In the event of rapidly proliferative disease use of hydroxyurea is permitted until 24 hours before the start of study treatment
• Clinical evidence of active CNS leukemia
• Patients with history of and/or current evidence of myocardial impairment (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in New York Heart Association Class III or IV staging
• Active and uncontrolled infection. Patients with a bacterial infection receiving treatment with antibiotics may be entered into the study if they are afebrile and hemodynamically stable for >72 hrs.
• Current evidence of invasive fungal infection (blood or tissue culture); active hepatitis C infection or known HIV infection
• Hypersensitivity to cytarabine, daunorubicin or liposomal products
• History of Wilson's disease or other copper-related disorder
• Patients with a history of severe toxicity related to receiving conventional dose cytarabine in first line treatment (approximately 100mg/m2/d for <7 days) are excluded. Patients who experienced unacceptable toxicities while receiving high dose cytarabine (approximately 3000mg/m2 for 6 doses) will not be treated again with the same regimen, but could be randomized to treatment with conventional dose cytarabine regimens where the risk of major toxicity is less.
• Woman who are pregnant or breast feeding