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CPI-613 and Hydroxychloroquine in Treating Patients with Recurrent High Risk Myelodysplastic Syndrome

Trial Status: In Review

This phase I / II trial studies the side effects and best dose of hydroxychloroquine and how well CPI-613 and hydroxychloroquine work in treating patients with high risk myelodysplastic syndrome that has come back after hypomethylating therapy. CPI-613 is thought to kill cancer cells by turning off their mitochondria. Mitochondria are used by cells to produce energy and are the building blocks needed to make more cells. By shutting off these mitochondria, CPI-613 deprives the cells of energy and other supplies that they need to survive and grow in your body. Hydroxychloroquine is an antimalarial drug. Hydroxychloroquine may make CPI-613 more effective in treating patients with myelodysplastic syndrome.

Inclusion Criteria

  • Histologically documented high risk MDS whose disease has failed to respond, progressed or relapsed while on a hypomethylating agent.
  • International Prognostic Scoring System risk (IPSS-R) score of intermediate, high or very high at time of enrollment.
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 3.
  • 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.
  • Aspartate aminotransferase (AST / serum glutamic-oxaloacetic transaminase [SGOT]) =< 3 x upper normal limit (UNL) (obtained =< 2 weeks prior to enrollment).
  • Alanine aminotransferase (ALT / serum glutamate pyruvate transaminase [SGPT]) =< 3 x UNL (obtained =< 2 weeks prior to enrollment).
  • Bilirubin =< 1.5 x UNL (obtained =< 2 weeks prior to enrollment).
  • Serum creatinine =< 1.5 x mg/dL or 133 umol/L (obtained =< 2 weeks prior to enrollment).
  • Albumin >= 2.0 g/dL or >= 20 g/L (obtained =< 2 weeks prior to enrollment).
  • Mentally competent, ability to understand and willingness to sign an Institutional Review Board (IRB)-approved written informed consent form.
  • Have access via central line (e.g., portacath).

Exclusion Criteria

  • 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 human immunodeficiency virus (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.

New York

Roswell Park Cancer Institute
Contact: Eunice Sue Wang
Phone: 716-845-3544

North Carolina

Wake Forest University Health Sciences
Contact: Bayard Lowery Powell
Phone: 336-716-4464


I. To determine the maximum tolerated dose (MTD) of the combination of 6,8-bis(benzylthio)octanoic acid (CPI-613) and hydroxychloroquine therapy for patients with high risk myelodysplastic syndrome (MDS) who have failed hypomethylating therapy.

II. To determine the overall response rate (complete remission (CR), marrow CR, partial remission (PR), hematologic improvement (HI)) of high risk MDS patients who have failed hypomethylating agents, treated with the combination of CPI-613 and the maximally tolerated dose of hydroxychloroquine.


I. To assess the safety of the combination.

II. To assess progression-free-survival (PFS).

III. To assess the overall survival of MDS patients who have failed hypomethylating agents treated with the combination of CPI-613 and hydroxychloroquine defined as the time from enrollment on study to death from any cause.

IV. To assess any changes in the frequency of blood transfusions.

OUTLINE: This is a phase I, dose-escalation study of hydroxychloroquine, followed by a phase II study.

Patients receive hydroxychloroquine orally (PO) and 6,8-bis(benzylthio)octanoic acid intravenously (IV) over 2 hours on days 1-5. Treatments repeat every 14 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 3, patients receive hydroxychloroquine PO and 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-5. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Wake Forest University Health Sciences

Principal Investigator
Bayard Lowery Powell

  • Primary ID WFBCCC 99119
  • Secondary IDs NCI-2019-02787
  • ID NCT03929211