A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies
- Conditions
- Relapsed/Refractory Mantle Cell LymphomaRelapsed/Refractory Acute Myeloid LeukemiaRelapsed/Refractory MyelodysplasiaRelapsed/Refractory MyelofibrosisAdenoid Cystic CarcinomaRefractory Chronic Myelomonocytic LeukemiaRelapsed/Refractory Advanced Solid TumorsRelapsed/Refractory Diffuse Large B-cell Lymphoma
- Interventions
- Registration Number
- NCT03886831
- Lead Sponsor
- Prelude Therapeutics
- Brief Summary
This is a Phase 1 cohort, dose-escalation, dose-expansion study of PRT543 in patients with advanced cancers who have exhausted available treatment options. The purpose of this study is to define a safe dose and schedule to be used in subsequent development of PRT543.
- Detailed Description
This is a multicenter, open-label, sequential-cohort, dose-escalation, dose-expansion Phase 1 study of PRT543 in patients with advanced cancers who have exhausted available treatment options. Enrollment will take place concurrently into two distinct patient groups (one for solid tumors/lymphomas and one for hematological malignancies). The study will consist of 2 parts, a dose escalation part, and once the recommended phase 2 dose (RP2D) has been determined, a cohort expansion part involving up to ten separate cohorts. For patients, the study will include a screening phase, a treatment phase, and a post treatment follow-up phase. An end-of-study visit will be conducted within 30 days after the last dose of PRT543.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 232
- Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome, acute myeloid leukemia or chronic myelomonocytic leukemia; or relapsed myelofibrosis. All malignancies must be refractory to established therapies
- Biomarker-selected solid tumors
- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
- Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
- Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use an effective method of contraception during the trial
- Primary malignancies of the Central Nervous System(CNS) or uncontrolled CNS metastases
- Requirement of pharmacologic doses of glucocorticoids
- Prior treatment with chimeric antigen receptor T cells (CAR-T cells)
- HIV positive; known active hepatitis B or C
- Known hypersensitivity to any of the components of PRT543
- Prior allogeneic bone marrow transplant; autologous hematopoietic transplantation less than 100 days since transplantation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description PRT543 PRT543 PRT543 will be administered orally
- Primary Outcome Measures
Name Time Method To determine the maximally tolerated dose (MTD) Baseline through approximately 2 years. The maximum tolerated dose (MTD) will be established for further investigation in participants with advanced malignancies who have failed prior treatments.
To describe dose limiting toxicities (DLT) of PRT543 Baseline through Day 28. Dose limiting toxicities (DLTs) will be evaluated during the first cycle
To determine the recommended phase 2 dose (RP2D) and schedule of PRT543 Baseline through approximately 2 years. The recommended phase 2 dose (RP2D) and optimal dosing schedule of PRT543 will be established for further investigation in participants with advanced malignancies who have failed prior treatments.
- Secondary Outcome Measures
Name Time Method To describe the adverse event profile and tolerability of PRT543 Baseline through approximately 2 years Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy
To determine the maximum observed plasma concentration (Cmax) of PRT543 Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1. PRT543 pharmacokinetics will be calculated including the maximum observed plasma concentration.
To determine the time to reach maximum observed plasma concentration (Tmax) of PRT543 Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1. PRT543 pharmacokinetics will be calculated including the time to reach maximum observed plasma concentration
Trial Locations
- Locations (23)
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
The Ohio State University and Wexner Medical Center
🇺🇸Columbus, Ohio, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
PLLC
🇺🇸Nashville, Tennessee, United States
UCSF Precision Cancer Medicine Building
🇺🇸San Francisco, California, United States
Christiana Care Health Services, Christiana Hospital
🇺🇸Newark, Delaware, United States
Florida Cancer Specialist
🇺🇸Sarasota, Florida, United States
Georgia Cancer Center at Augusta University
🇺🇸Augusta, Georgia, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Florida Cancer Specialists
🇺🇸Lake Mary, Florida, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Norton Cancer Institute, St. Matthews Campus
🇺🇸Louisville, Kentucky, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Atlantic Health System / Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States