8-Chloroadenosin v léčbě pacientů s recidivující nebo refrakterní akutní myeloidní leukémií

Inclusion Criteria:

• All subjects must have the ability to understand and the willingness to sign a written informed consent

• Patients must have a life expectancy of > 3 months

• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Patients must have a diagnosis of AML as per World Health Organization (WHO) Classification of Hematologic Neoplasms

• Patients must meet one of the three treatment history criteria:

  • Relapsed AML who have failed at least 1 line of salvage therapy
  • De novo AML who have not achieved CR after 2 lines of therapy
  • AML evolving from myelodysplastic syndrome (MDS) or myeloproliferative disorder who have failed hypomethylating agent or induction chemotherapy
  • Patients who have relapsed after allogeneic hematopoietic cell transplant (HCT) are eligible if they are at least 3 months after HCT, do not have active graft vs. host disease (GVHD) and are off immunosuppression except for maintenance dose of steroids (prednisone 10 mg/day or less)

• At least 2 weeks from prior chemotherapy or radiation therapy to time of start of treatment, except for hydroxyurea or corticosteroid therapy which may be continued through cycle 1

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)

• Total bilirubin =< 1.5 X ULN

• Corrected QT (QTc) =< 480 ms

• Calculated creatinine clearance (CrCl) >= 50 mL/min per 24 hour urine collection or the Cockcroft-Gault formula

• Negative serum or urine beta-human chorionic gonadotropin (beta-HCG) test (female of childbearing potential only), to be performed locally within the screening period

• Agreement by females of childbearing potential and sexually active males to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for three months following duration of study participation; the effects of study treatment on a developing fetus have the potential for teratogenic or abortifacient effects; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

Exclusion Criteria:

• Current or planned use of other investigational agents, or concurrent biological chemotherapy, or radiation therapy during the study treatment period
• Expected to undergo HCT within 120 days of enrollment
• Current or planned use of agents that prolong or suspected to prolong QTc
• Diagnosis of acute promyelocytic leukemia
• Active central nervous system leukemia
• Active fungal infection or bacterial sepsis
• Active peptic ulcer disease
• History of heart failure or cardiac arrhythmia
• Other active malignancy except for localized skin cancer, bladder, prostate, breast or cervical carcinoma in situ
• Pregnant women and women who are lactating; 8-chloro-adenosine is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 8-chloro-adenosine, breastfeeding should be discontinued if the mother is treated with 8-chloro-adenosine
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)