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

NCT ID: NCT03929211

Last Updated: 2021-04-14

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-31
• Study Completion Date: 2027-07-31

Brief 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.

Detailed Description

Primary Objective(s):

• To determine the Maximum Tolerated Dose (MTD) of the combination of CPI-613 and Hydroxychloroquine therapy for patients with high risk MDS who have failed hypomethylating therapy.
• 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

Secondary Objective(s):

• To assess the safety of the combination
• To assess progression-free-survival (PFS)
• 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 enrolment on study to death from any cause.
• 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.

Conditions

Myelodysplastic Syndromes; Progressive Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CPI-613 and hydroxychloroquine

The initial phase of the study will be a dose escalation of hydroxychloroquine from 600 mg to 1,200 mg orally flat dose given 2 hours before the CPI-613 infusion on days 1-5 of every 28 days. CPI-dose will be 2,000 mg/m² and will not be escalated.

Group Type: EXPERIMENTAL

CPI-613

Intervention Type: DRUG

Given intravenously, CPI-613 dose will be 2,000 mg/m² and will not escalate.

Hydroxychloroquine

Intervention Type: DRUG

Given by mouth, hydroxychloroquine will be dose escalated from 600 mg to 1,200 mg orally given 2 hours before the CPI-613 infusion on days 1-5 of every 28 day cycle in a 3+3 dose escalation design.

Interventions

CPI-613

Given intravenously, CPI-613 dose will be 2,000 mg/m² and will not escalate.

Intervention Type: DRUG

Hydroxychloroquine

Given by mouth, hydroxychloroquine will be dose escalated from 600 mg to 1,200 mg orally given 2 hours before the CPI-613 infusion on days 1-5 of every 28 day cycle in a 3+3 dose escalation design.

Intervention Type: DRUG

Other Intervention Names

6,8-Bis(benzylthio)octanoic Acid; 118-42-3, hydroxychloroquine, HYDROXYCHLOROQUINE, Hydroxychloroquine

Eligibility Criteria

Inclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayard Powell, MD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Countries

United States

Other Identifiers

WFBCCC 99119

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2019-02787

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00057945

Identifier Type: -

Identifier Source: org_study_id