CPI-613 and Hydroxychloroquine for Patients With High Risk Myelodysplastic Syndrome
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|ClinicalTrials.gov Identifier: NCT03929211|
Recruitment Status : Not yet recruiting
First Posted : April 26, 2019
Last Update Posted : February 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndromes Progressive Disease||Drug: CPI-613 Drug: Hydroxychloroquine||Phase 1 Phase 2|
- 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
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of CPI-613 and Hydroxychloroquine for Patients With High Risk MDS Who Have Failed Hypomethylating Therapy|
|Estimated Study Start Date :||April 2020|
|Estimated Primary Completion Date :||September 2021|
|Estimated Study Completion Date :||July 2026|
Experimental: 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.
Given intravenously, CPI-613 dose will be 2,000 mg/m² and will not escalate.
Other Name: 6,8-Bis(benzylthio)octanoic Acid
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.
Other Name: 118-42-3, hydroxychloroquine, HYDROXYCHLOROQUINE, Hydroxychloroquine
- Number of Dose Limiting Toxicities [ Time Frame: 4 weeks ]Dose-limiting toxicities assessed in order to be able to establish the maximum tolerable dose for the combination of CPI-613 and Hydroxychloroquine therapy for patients with high risk myelodysplastic syndrome who have failed hypomethylating therapy. Using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 for adverse event reporting (Grade 1 (Mild) - 5 (Death) as well as expectedness (unexpected/expected) and attribution (definitely related to study treatment to unrelated to study treatment).
- Overall Response Rate [ Time Frame: 4 weeks ]Measurements for response criteria will be based upon the Modified International Working Group (IWG) 2006 response criteria for altering natural history of myelodysplastic syndrome. Overall response rates criteria - complete remission (CR), partial response (PR) marrow CR, hematologic improvement (HI), or stable disease, failure, relapse after complete response or partial response, cytogenetic response, disease progression and survival) of high risk myelodysplastic syndrome patients who have failed hypomethylating agents treated with the combination of CPI-613 and the maximally tolerated dose of hydroxychloroquine.
- Proportion of Patients with Toxicities [ Time Frame: 4 weeks ]Toxicity profiles of participants during the trial to assess the safety of the combination of CPI-613 and hydroxychloroquine will be presented in tables that describe the number and proportion of patients observed with toxicities.
- Progression-free-survival [ Time Frame: Up to 5 years or until death ]Progression-free-survival is defined as the duration of time from the start of treatment to the time of progression, death, or date of last contact; those lost to follow-up will be censored. Kaplan-Meier survival curves to examine progression free survival in participants will be created.
- Overall Survival [ Time Frame: Up to 5 years or until death ]Overall survival of myelodysplastic syndrome 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.
- Changes in the Frequency of Blood Transfusions [ Time Frame: Baseline to approximately 6 months ]The investigators will assess for each participant the number of blood transfusions needed and create tables to display the number and timing of blood transfusions that occur.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03929211
|Contact: Brittany Mabe, RNfirstname.lastname@example.org|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator: Eunice Wang|
|United States, North Carolina|
|Wake Forest Baptist Comprehensive Cancer Center|
|Winston-Salem, North Carolina, United States, 27157|
|Principal Investigator: Bayard Powell|
|Principal Investigator:||Bayard Powell, MD||Wake Forest University Health Sciences|