A Phase 1 Study to Evaluate the Safety and Pharmacokinetic Profiles of CB-5339 in Participants With Relapsed/Refractory Acute Myeloid Leukemia or Relapsed/Refractory Intermediate or High Risk Myelodysplastic Syndrome
Brief SummaryThis is a multicenter, open-label Phase 1 study of orally administered CB-5339 in participants with R/R AML or participants with R/R intermediate- to high-risk MDS.
Detailed DescriptionThis is a multicenter, open-label Phase 1 study of orally administered CB-5339 in participants with R/R AML or participants with R/R intermediate- to high-risk MDS. The study will include two parts:1) a Dose Escalation phase in participants with R/R AML, or R/R intermediate- to high-risk MDS and 2) a Dose Expansion phase in participants with R/R AML for whom there is no standard of care therapy available that is likely to lead to disease remission. Additional cohorts for participants with R/R intermediate- to high-risk MDS following hypomethylating agents or other AML cohorts may be added at a later time.
Inclusion and Exclusion Criteria
- Male or female and ≥ 18 years of age at the time of signing the consent form
- One of the following advanced hematologic malignancies including: - Relapsed or refractory AML as defined by 2016 WHO criteria and are not candidates for curative therapies such as allogeneic hematopoietic cell transplant or for whom there is no standard of care therapy available that is likely to lead to disease remission according the investigator - MDS high-very high risk by the revised international scoring system for evaluating prognosis in myelodysplastic syndromes that is recurrent or refractory or the participant is intolerant to established therapy known to provide clinical benefit for their condition (e.g., relapsed following treatment with hypomethylating agent or lack of response after > 4 cycles), according to treating physician. Potential participants who meet the criteria for intermediate risk may be considered with approval by the medical monitor if the participant has severe cytopenia(s) and/or elevated bone marrow blast counts.
- Adequate organ function defined as: - Serum creatinine ≤1.5 mg/dL or an estimated glomerular filtration rate of ≥60 mL/min as calculated by the Cockcroft-Gault glomerular filtration rate equation - Total bilirubin ≤ 1.5 × the upper limit of normal (ULN) unless considered due to Gilbert's disease or leukemic disease - Aspartate aminotransferase (AST) ≤3 × the ULN; alanine aminotransferase (ALT) ≤3 × the ULN. Levels of AST and/or ALT ≤5 × the ULN may be acceptable for participants with known leukemic involvement of the liver after discussion with the study medical monitor
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If of childbearing potential, agree to use an effective barrier method of birth control (i.e., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy during the
- Female participants of childbearing potential need a negative serum or urine pregnancy test within 7 days of study enrollment. Non-childbearing is defined as ≥ 1 year postmenopausal or surgically sterilized
- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
- Acute promyelocytic leukemia with t(15;17)(q22;q12); or abnormal promyelocytic leukemia/retinoic acid receptor alpha (PML-RARA).
- Participants with clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening.
- Participants with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
- Concomitant malignancy, requiring active treatment, except for basal-cell or squamous cell carcinoma of the skin, carcinoma-in-situ of the uterine cervix, or localized prostate cancer.
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.