PRT1419 as Monotherapy or in Combination With Azacitidine or Venetoclax in R/R Myeloid or B-cell Malignancies

January 29, 2024 updated by: Prelude Therapeutics

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a multicenter, open-label, dose-escalation, Phase 1 study of PRT1419, a MCL-1 inhibitor, evaluating participants with acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome (MDS), MDS/myeloproliferative neoplasm (MPN) overlap syndrome, chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), and B-cell non-hodgkin lymphoma (NHL) including marginal zone lymphoma, follicular lymphoma or mantle cell lymphoma. Participants in study will receive PRT1419 as monotherapy or in combination with either Azacitidine (AZA) or Venetoclax (VEN). The study includes multiple dose escalations and expansion cohorts for RP2D confirmation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Orange City, Florida, United States, 32763
        • Mid Florida Hematology and Oncology Center
      • Orlando, Florida, United States, 32804
        • AdventHealth Bone and Marrow Transplant Center
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • American Oncology Partners of Maryland, PA
    • New Jersey
      • Brick, New Jersey, United States, 08724
        • New Jersey Center for Cancer Research
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center - Main Campus
      • Port Jefferson Station, New York, United States, 11776
        • North Shore Hematology Oncology Associates. DBA New York Cancer and Blood Specialists
    • Ohio
      • Canton, Ohio, United States, 44718
        • Gabrail Cancer Center Research
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University, Sidney Kimmel Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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:

    1. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    2. Adequately treated cervical or breast carcinoma in situ without evidence of disease
    3. 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
    4. Other malignancy treated with curative intent with no known active disease for > 2 years prior to enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: PRT1419 Monotherapy
PRT1419 will be administered by intravenous infusion once weekly on a 28-day treatment cycle at the dose level assigned.
Drug: PRT1419
PRT1419 will be administered by intravenous infusion
Experimental: PRT1419/Azacitidine Combination
PRT1419 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.
Drug: PRT1419
PRT1419 will be administered by intravenous infusion
Drug: Azacitidine
Azacitidine will be administered by intravenous or subcutaneous
Experimental: PRT1419/Venetoclax Combination
PRT1419 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.
Drug: PRT1419
PRT1419 will be administered by intravenous infusion
Drug: Venetoclax
Venetoclax will be administered orally

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose limiting toxicities (DLT) of PRT1419
Time Frame: Baseline through Day 28
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
Time Frame: Baseline through approximately 3 years
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
Time Frame: Baseline through approximately 2 years
The MTD/RP2D will be established for further investigation in participants with advanced hematologic malignancies
Baseline through approximately 2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: maximum observed plasma concentration
Time Frame: Baseline through approximately 3.5 years
PRT1419 pharmacokinetics will be calculated by 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
Time Frame: Baseline through approximately 3.5 years
PRT1419 pharmacokinetics will be calculated by time to maximal plasma concentration (Tmax)
Baseline through approximately 3.5 years
Pharmacokinetic profile of PRT1419 monotherapy and in combination with AZA or VEN: Area under the curve
Time Frame: Baseline through approximately 3.5 years
PRT1419 pharmacokinetics will be calculated by area under the plasma concentration x time curve (AUC) from h 0 to the last measurable time point (AUC0-last)
Baseline through approximately 3.5 years
Safety and tolerability of PRT1419 in combination with AZA and VEN: AEs, SAEs, CTCAE assessments
Time Frame: Baseline through approximately 3 years
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
Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Overall response rate (ORR)
Time Frame: Baseline through approximately 3.5 years
Anti-tumor activity of PRT1419 based on the measurement of objective response rate (ORR) according to the disease-specific response criteria for malignancies under study
Baseline through approximately 3.5 years
Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Progression-free survival (PFS)/event free survival (EFS)
Time Frame: Baseline through approximately 3.5 years
Duration from Day 1 to the earliest date of first disease progression, as assessed by the investigator according to the disease-specific response criteria for malignancies under study, or death due to any cause
Baseline through approximately 3.5 years
Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Duration of response (DOR)
Time Frame: Baseline through approximately 3.5 years
Duration from time of first observed response (CR or PR) to the earliest date of disease progression, as assessed by the investigator according to the disease-specific response criteria for malignancies under study, or death due to any cause
Baseline through approximately 3.5 years
Anti-tumor activity of PRT1419 monotherapy and in combination with AZA and VEN: Overall survival (OS)
Time Frame: Baseline through approximately 3.5 years
Duration from Day 1 until death due to any cause
Baseline through approximately 3.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Prelude Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 22, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 19, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 19, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 25, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 4, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 31, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRT1419-03

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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