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PRT1419 as Monotherapy or in Combination With Azacitidine or Venetoclax in R/R Myeloid or B-cell Malignancies
A Phase 1, Open-Label, Multicenter, Dose Escalation Study of PRT1419 Injection as Monotherapy or in Combination With Azacitidine or Venetoclax in Patients With Relapsed/Refractory Myeloid or B-cell Malignancies
1 other identifier
interventional
21
1 country
9
Brief Summary
This is a Phase 1 dose-escalation study of PRT1419, a myeloid cell leukemia-1 (MCL-1) inhibitor, in participants with selected relapsed/refractory myeloid or B-cell malignancies. The purpose of this study is to evaluate the safety and tolerability of PRT1419 monotherapy and in combination with either azacitidine or venetoclax, describe any dose limiting toxicities (DLTs), define the dosing schedule, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Mar 2022
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 25, 2021
CompletedFirst Posted
Study publicly available on registry
November 4, 2021
CompletedStudy Start
First participant enrolled
March 22, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 19, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
January 19, 2024
CompletedJanuary 31, 2024
January 1, 2024
1.8 years
October 25, 2021
January 29, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Dose limiting toxicities (DLT) of PRT1419
Dose limiting toxicities will be evaluated over the 28-day observation period
Baseline through Day 28
Safety and tolerability of PRT1419: AEs, SAEs, CTCAE assessments
Safety and tolerability will be assessed by recording adverse events (AEs), serious adverse events (SAEs), and DLTs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Baseline through approximately 3 years
Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) and schedule of PRT1419
The MTD/RP2D will be established for further investigation in participants with advanced hematologic malignancies
Baseline through approximately 2 years
Secondary Outcomes (8)
Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: maximum observed plasma concentration
Baseline through approximately 3.5 years
Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: Time to maximal plasma concentration
Baseline through approximately 3.5 years
Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: Area under the curve
Baseline through approximately 3.5 years
Safety and tolerability of PRT1419 in combination with AZA and VEN: AEs, SAEs, CTCAE assessments
Baseline through approximately 3 years
Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Overall response rate (ORR)
Baseline through approximately 3.5 years
- +3 more secondary outcomes
Study Arms (3)
PRT1419 Monotherapy
EXPERIMENTALPRT1419 will be administered by intravenous infusion once weekly on a 28-day treatment cycle at the dose level assigned.
PRT1419/Azacitidine Combination
EXPERIMENTALPRT1419 will be administered by intravenous infusion once weekly on a 28-day treatment cycle at the dose level assigned and Azacitidine will be administered by intravenous or subcutaneous on Days 1 through 7 (or alternatively on Days 1 through 5, 8 and 9) of each 28-day treatment cycle.
PRT1419/Venetoclax Combination
EXPERIMENTALPRT1419 will be administered by intravenous infusion once weekly on a 28-day treatment cycle at the dose level assigned and Venetoclax will be administered orally after either a 3-day or 5-week ramp-up period to reach 400 mg daily administration, prior to commencing PRT1419 administration.
Interventions
PRT1419 will be administered by intravenous infusion
Azacitidine will be administered by intravenous or subcutaneous
Eligibility Criteria
You may qualify if:
- Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations (including contraception requirements), and other study procedures
- Refractory/relapsed disease, having progressed on prior treatment, and without access to further approved therapies or ineligible for approved therapies, in one of the following disease categories: AML, CMML, MDS, MDS/MPN Overlap Syndrome, CLL/SLL, and B-cell NHLs
- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 to 2
- Adequate organ function (hematology, hepatic, renal, and coagulation)
You may not qualify if:
- Active inflammatory disorders of the gastrointestinal tract, a history of bariatric surgery or other disorders with the potential for GI malabsorption
- Cardiac function compromise, as assessed by echocardiogram or protocol-specified biochemical markers of cardiac damage, or protocol-defined clinically significant heart disease
- History of cerebrovascular accident or transient ischemic attack, within 6 months of screening. Participants with a history of pulmonary embolism must not be symptomatic at enrollment
- Undergone hematopoietic stem-cell transplantation (HSCT) within the last 90 days or have graft-versus-host disease (GVHD) Grade \> 1 at study entry
- Uncontrolled intercurrent illnesses, poorly controlled hypertension or dyslipidemias, Unstable central nervous system (CNS) metastases
- Treatment with either OATP1B1, OATP1B3 substrates or strong inhibitors of CYP2C8, CYP3A4, and any medication contraindicated in combination with AZA or VEN
- Prior exposure to an MCL-1 inhibitor
- Within 5 half-lives or 14 days (whichever is longer) following the last systemic anti-cancer therapy
- History of another malignancy except for:
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated cervical or breast carcinoma in situ without evidence of disease
- Asymptomatic prostate cancer without known metastatic disease and no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for \>1 year prior to enrollment
- Other malignancy treated with curative intent with no known active disease for \> 2 years prior to enrollment
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
Mid Florida Hematology and Oncology Center
Orange City, Florida, 32763, United States
AdventHealth Bone and Marrow Transplant Center
Orlando, Florida, 32804, United States
American Oncology Partners of Maryland, PA
Bethesda, Maryland, 20817, United States
New Jersey Center for Cancer Research
Brick, New Jersey, 08724, United States
Memorial Sloan Kettering Cancer Center - Main Campus
New York, New York, 10065, United States
North Shore Hematology Oncology Associates. DBA New York Cancer and Blood Specialists
Port Jefferson Station, New York, 11776, United States
Gabrail Cancer Center Research
Canton, Ohio, 44718, United States
Thomas Jefferson University, Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 25, 2021
First Posted
November 4, 2021
Study Start
March 22, 2022
Primary Completion
January 19, 2024
Study Completion
January 19, 2024
Last Updated
January 31, 2024
Record last verified: 2024-01