Clinical Study of PM01183 in Patients With Acute Leukemia or Relapsed/Refractory Myelodysplastic Syndrome

Inclusion Criteria:

• Voluntarily signed and dated written informed consent
• Age ≥ 18 years.

• Patients must have a previous cytological or histological diagnosis of:

  • Relapsed or primary refractory non-M3 acute myeloid leukemia (AML) by the World Health Organization (WHO) criteria (irrespective of the number of prior regimens), either de novo or secondary [i.e., secondary to myelodysplastic syndromes (MDS), myeloproliferative neoplasms or previous chemotherapy for another condition].
  • Untreated AML in patients ≥ 65 years of age, if patients are not candidates for standard induction chemotherapy or have poor risk AML (i.e., secondary AML or AML with adverse cytogenetics or complex karyotype).
  • Accelerated or blastic phase chronic myeloid leukemia (CML, with progressive disease despite treatment with BCR-ABL kinase inhibitors), or chronic myelomonocytic leukemia (CMML).
  • Relapsed or refractory acute lymphoblastic leukemia (ALL) by WHO criteria.

• Patients must have the following laboratory values prior to the start of treatment:

  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) range of values, unless due to elevated indirect bilirubin (e.g.,Gilbert's syndrome or hemolysis).
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN.
  • Alkaline phosphatase (AP) ≤ 2.5 x ULN.
  • Albumin ≥ 2.5 g/dl.
  • Calculated creatinine clearance (CrCl) ≥ 30 ml/min (using Cockcroft and Gault's formula).
  • Creatine phosphokinase (CPK) ≤ 2.5 x ULN.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
• Negative pregnancy test for women of childbearing potential.

Exclusion Criteria:

• Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods throughout the treatment period and for six months after discontinuation of treatment.
• Patients who plan to undergo allogeneic BM transplantation within four weeks.

• Other relevant diseases or adverse clinical conditions:

  • History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
  • Symptomatic or unstable cardiac arrhythmias, and/or prolonged QT-QTc grade ≥ 2.
  • History of significant neurological or psychiatric disorders that may affect the patient's compliance with the protocol assessments.
  • Active uncontrolled infection.
  • Myopathy or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 x ULN in two different determinations performed one week apart).
  • Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis).
  • Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
• Hematopoietic allogeneic stem cell transplantation within the last four months and/or active graft versus host disease, or prior autologous transplantation within the last four weeks.
• Patients known to be human immunodeficiency virus (HIV) positive.
• Cytotoxic chemotherapy within the last two weeks; radiation therapy within the last two weeks; biologic agents, including hematopoietic growth factors, within the last week; hydroxyurea, imatinib, corticosteroids and arsenic trioxide should be discontinued at least 24 hours prior to first study drug administration.
• Treatment with any investigational product in the ≤ 5 half-lives period prior to inclusion in the study, or 30 days after therapy (in case of unknown half-life), unless evidence of rapid proliferating disease and upon discussion with the Sponsor.
• Known hypersensitivity to any of the components of the drug product (DP).