L-Annamycin for Injection in Combination With Cytarabine Injection as Second Line Therapy for Remission Induction in Adult Subjects With Refractory/Relapsed AML

This pivotal phase 2/3, multi-center, adaptive design study of L-Annamycin for Injection in combination with Cytarabine Injection as second line therapy for remission induction in adult subjects with refractory/relapsed AML is divided into two parts, Part A and Part B.

Part A (Determination of Optimal Dosage Regimen) Part A of this study is a randomized, double-blind, placebo-controlled (RDBPC), efficacy, safety, tolerability, and pharmacokinetics study comparing two dose levels of L Annamycin for Injection (190 versus 230 mg/m2/day) in combination with Cytarabine Injection (2.0 g/m2/day) versus placebo in combination with Cytarabine Injection to identify the optimal dosage regimen as second line therapy for remission induction in adult subjects with refractory/relapsed AML.

Seventy-five to ninety subjects with a pathologically confirmed diagnosis of AML who have refractory/relapsed AML after having received only one prior line of therapy will be enrolled in Part A. A prior line of therapy will be defined as the planned therapy consisting of one or more cycles of episodic treatment or a defined period of continuous treatment. This may consist of single-agent or combination therapy as well as a planned sequence of treatment phases. For example, first-line treatment of AML with induction, consolidation, and allogeneic hematopoietic stem cell transplantation (alloHSCT) is considered one line of therapy. A line of therapy ends when the patient fails to achieve a response within a prespecified period (refractory) or relapses after achieving CR. For the purpose of confirming refractory AML at screening, refractory disease will be defined as CR not being achieved after first line therapy \[i.e., after 1 cycle of intensive therapy or 180 days after commencing less-intensive therapy (shorter durations of less-intensive therapy may be considered for refractory disease on a case by case basis after discussion between the PI and Medical Monitor)\]. Subjects who meet all eligibility criteria after the completion of both screening and baseline assessments will be enrolled. Initially, 45 subjects will be randomized 1:1:1 to one of the three treatment arms listed below (i.e.,approximately 15 per treatment arm). Randomization will be stratified by continent. Depending on the outcome of the first interim analysis (see further below), additional subjects will either be randomized 1:1:1 to one of the three treatment arms listed below (for a total of approximately 30 per treatment arm in Part A) randomized 1:1 to either placebo in combination with Cytarabine Injection (Treatment Arm 1) or the L-Annamycin for Injection in combination with Cytarabine Injection arm that was selected to continue after the first interim analysis (i.e., Treatment Arm 2 or 3) (for a total of approximately30 per treatment arm in Part A, except for the arm that is dropped after the first interim analysis, which will have a total of approximately ≤15 and ≤30, depending on how many subjects were enrolled at the point the decision to drop the arm occurs).