Open-Label, Dose-Escalating, Clinical and Pharmacokinetic Phase I Study of PM01183 in Patients With Advanced Acute Leukemia.
- 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
- 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
- Creatine phosphokinase (CPK) ≤ 2.5 x ULN.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
- Negative pregnancy test for women of childbearing potential.
- 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
- Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic
- 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
- 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).