CPI-613 and Hydroxychloroquine for Patients With High Risk Myelodysplastic Syndrome

• Status: Withdrawn
• Trial end date: 2027-07-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase 1/2 study of the combination of CPI-613 and hydroxychloroquine for the treatment of high risk myelodysplastic syndrome patients who have failed a hypomethylating agent.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Wake Forest University Health Sciences
• Collaborator: National Cancer Institute (NCI)
• Treatments: Hydroxychloroquine

Criteria

Inclusion Criteria:

Patients must meet all of the following inclusion criteria before enrollment:

• Histologically documented high risk MDS whose disease has failed to respond, progressed or relapsed while on a hypomethylating agent.

• IPSS-R score of Intermediate, high or very high at time of enrollment

• ECOG Performance Status of ≤3.

• Men and women 18 years of age or older.

• Expected survival >2 months.

• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study, and must have a negative serum or urine pregnancy test within 1 week prior to treatment initiation.

• Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists.

• Patients must have fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities. Patients with persisting, non-hematologic, non-infectious toxicities from prior treatment ≤ Grade 2 are eligible, but must be documented as such.

• Laboratory values obtained ≤2 weeks prior to enrollment must demonstrate adequate hepatic function, renal function, and coagulation as defined below:

• Aspartate aminotransferase [AST/SGOT] ≤3x upper normal limit [UNL]

• Alanine aminotransferase [ALT/SGPT] ≤3x UNL

• Bilirubin ≤1.5x UNL

• Serum creatinine ≤1.5 mg/dL or 133 μmol/L

• Albumin ≥ 2.0 g/dL or ≥ 20 g/L.

• Mentally competent, ability to understand and willingness to sign an IRB-approved written informed consent form.

• Have access via central line (e.g., portacath).

Exclusion Criteria:

• Patients with the following characteristics are excluded:

• Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, symptomatic coronary artery disease, myocardial infarction within the past 3 months, uncontrolled cardiac arrhythmia, pericardial disease or New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity.

• Patients with active central nervous system (CNS) or epidural tumor.

• Any active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease).

• Any condition or abnormality which may, in the opinion of the investigator, compromise his or her safety.

• Pregnant women, or women of child-bearing potential not using reliable means of contraception.

• Fertile men unwilling to practice contraceptive methods during the study period.

• Lactating females.

• Life expectancy less than 2 months.

• Unwilling or unable to follow protocol requirements.

• Evidence of ongoing uncontrolled serious infection.

• Requirement for immediate palliative treatment of any kind including surgery.

• Patients with uncontrolled HIV infection. (Note: Patients with known HIV infection are excluded because patients with an immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, and because there may be unknown or dangerous drug interactions between CPI-613 and anti-retroviral agents used to treat HIV infections).

• Patients who have received radiotherapy, surgery, treatment with cytotoxic agents (except a hypomethylating agent, i.e. azacytidine or decitabine), treatment with biologic agents, immunotherapy, or any other anti-cancer therapy of any kind, or any other standard or investigational treatment for their cancer, or any other investigational agent for any indication, within the past 2 weeks prior to initiation of CPI-613 treatment.

• Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months.