The goal of this trial in Phase I is to determine the maximally tolerated dose (MTD) of hydroxychloroquine in combination with devimistat in patients with relapsed or refractory Clear Cell Sarcomas of the Soft Tissue and to describe the full toxicity profile. In Phase II, the goal is to evaluate the response rate \[Complete Rate (CR) + Partial Rate (PR)\] of the combination of devimistat and hydroxychloroquine in patients with relapse or refractory Clear Cell Sarcoma of the Soft Tissue and to evaluate the PK and PK/PD profiles for efficacy and safety of the combination of devimistat and hydroxychloroquine.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
16
dosing regimen was 600mg hydroxychloroquine PO followed 2 hours later by 2,000 mg/m2 of CPI-613 by central IV infusion over 2 hours followed by 600 mg hydroxychloroquine PO 12 hours following the initial dose daily on days 1 through 5 of every 28 days. Starting dose of 80% of the maximum tolerated (MTD) identified in patients ≥ 45 kg for patients \< 45 kg
City of Hope
Duarte, California, United States
University of Kansas Medical Center
Kansas City, Kansas, United States
University of Michigan
Ann Arbor, Michigan, United States
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, United States
Clevland Clinic
Ohio City, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Vanderbilt University Medical Centrer
Nashville, Tennessee, United States
Seattle Children's Hospital
Seattle, Washington, United States
MTD (Phase I)
To determine the maximally tolerated dose (MTD) of hydroxychloroquine in combination with devimistat in mg/m2 based on patient body weight in patients with relapsed or refractory fusion-positive sarcomas and relapsed or refractory clear cell sarcoma.
Time frame: 6 months
Toxicity (Phase I)
Dose-limiting toxicities assessed in order to be able to establish the maximum tolerable dose for the combination of CPI-613 and Hydroxychloroquine 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).
Time frame: 6 months
ORR (Overall Response rate): CR +PR (Phase II)
Overall response rate is defined as the proportion of patients who achieve a best overall response complete response or partial response during or following study treatment
Time frame: 12 months
DOR (Duration of Response)
It is the interval from date of initial documented response (CR or PR) to the first documented date of disease progression or death.
Time frame: 12 months
PFS (Progression Free Survival)
It is defined as the duration from the date of enrollment to the date of progressive disease or death from any cause.
Time frame: 12 months
OS (Overall Survival)
Defines as the time from randomization to the date of death due to any cause.
Time frame: 12 months
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