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

Prior treatment

• Has prior or current diagnosis of acute promyelocytic leukemia (APL) or myelodysplastic syndrome (MDS)/AML
• Received prior mediastinal radiotherapy.
• Has evidence of mucositis/stomatitis at screening or baseline, or has history of severe (≥Grade 3) mucositis/stomatitis from prior therapy.
• Has received prior treatment with L-asparaginase.
• Has received a total cumulative prior anthracycline dose of \> 300 mg/m2 (daunorubicin equivalent dose).

Other illness

• Has any condition that, in the opinion of the PI, places the subject at unacceptable risk if he/she were to participate in the study.
• Known hypersensitivity to anthracyclines, cytarabine, the excipients of L Annamycin for Injection or Cytarabine Injection, or contrast media that may be used for the protocol-specified GLS assessments.

Lab values

• Has impaired cardiac function, including any of the following:
  • Abnormal LVEF at screening \[per American College of Cardiology, normal LVEF is 50 to 70%
  • Valvular heart disease.
  • Severe, uncontrolled hypertension.
  • Uncontrolled cardiac arrhythmias.
  • Recent (≤6 months prior to screening) myocardial infarction.
  • Unstable angina.
  • Symptomatic congestive heart failure.
  • New York Heart Association (NYHA) classification of 3 or 4.
  • QT interval/corrected QT (QTc) interval \>480 msec at screening.
  • History of additional risk factors for torsade des pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
  • . Use of concomitant medications with known risk of Torsades de Pointes (TdP) (i.e., drugs that prolong the QT interval and that are clearly associated with a known risk of TdP, even when taken as recommended; refer to Appendix G for examples of such drugs), unless in the clinical judgement of the PI, the medication is imperative and can be used safely with adequate monitoring.
• Has clinically relevant serious comorbid medical conditions including, but not limited to, active infection, chronic obstructive or chronic restrictive pulmonary disease, history of positive status for human immunodeficiency virus (virus detected in serum) hepatitis B or hepatitis C with current serious symptoms or signs of underlying chronic infection or psychiatric illness/social situations that would limit compliance with study requirements.

Other

• Has central nervous system involvement.
• Pregnant or breastfeeding.
• Has relapsed or refractory AML with a FLT3 mutation, unless resides in a country where gilteritinib is not available.

• Has a pathologically confirmed diagnosis of AML per the 2022 International Consensus Classification (ICC) as adopted in the European LeukemiaNet (ELN) 2022 recommendations for the diagnosis and management of AML. The tests and procedures used to establish the diagnosis of AML should be consistent with the ELN's 2022 recommendations
• Has refractory/relapsed AML after having received only one prior line of therapy\*.
  • \*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 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 \[i.e., after 1 cycle of intensive therapy or 180 days after commencing less-intensive therapy (shorter durations of less-intensive therapy may be considered for refractory disease on a case by case basis after discussion between the PI and Medical Monitor)\].
• Between 18 and 80 years of age (inclusive) at the time of signing the informed consent form (ICF).
• Has received no chemotherapy, radiation, or major surgery within 2 weeks prior to the first randomized dose of study drug or has recovered from the toxic side effects of that therapy. Hydroxyurea to control white blood cell (WBC) count, supportive measures, and prophylaxes as required under the protocol will be allowed. Treatment of opportunistic or other infections with antibiotics, antifungals, and/or antiviral agents, including therapy for meningeal disease (i.e., intrathecal chemotherapy), per institutional standards of care will be allowed during this period, as long as the symptoms of infection have resolved by 1 week prior to the first dose of randomized study drug.
• Has received no investigational therapy within 4 weeks prior to the first randomized dose of study drug.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at screening.
• Has a life expectancy of greater than six weeks at screening.
• Has adequate laboratory results at screening including the following:
  • Total bilirubin ≤2.0 times the upper limit of normal (ULN). For subjects with leukemic involvement or Gilbert Syndrome, total bilirubin must be ≤3.0 ULN.
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase \<3.5 times the ULN. For subjects with organ involvement, AST, ALT, and alkaline phosphatase must be ≤4.5 times the ULN.
  • Creatinine clearance ≥60 mL/min (using Cockcroft-Gault equation).
• Can understand and sign the ICF, can communicate with the PI, and can understand and comply with the requirements of the protocol.
• For women of childbearing potential (WCBP): Must have a negative serum beta human chorionic gonadotropin (ß-hCG) pregnancy test within 72 hours prior to the first randomized dose of study drug.
• For WCBP: Must agree to not donate ova and use a highly effective method of birth control from the time of informed consent through 6 months after their last randomized dose of study drug.
• For males with partners who are WCBP: Must agree to not donate sperm and use a highly effective method of birth control from the time of informed consent through 6 months after their last randomized dose of study drug.