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A Study of PRT1419 Injection in Patients With Relapsed/Refractory Hematologic Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05107856
Recruitment Status : Recruiting
First Posted : November 4, 2021
Last Update Posted : April 8, 2022
Sponsor:
Information provided by (Responsible Party):
Prelude Therapeutics

Study Description
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Brief Summary:
This is a Phase 1 dose-escalation study of PRT1419, a myeloid cell leukemia 1 (MCL1) inhibitor, in patients with relapsed/refractory hematologic malignancies. The purpose of this study is to define the dosing schedule, maximally tolerated dose and/or estimate the optimal biological dose to be used in subsequent development of PRT1419.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia Myelodysplastic Syndrome Myeloproliferative Neoplasm Drug: PRT1419 Phase 1

Detailed Description:
This is a multicenter, open-label, dose-escalation Phase 1 study of PRT1419, a MCL1 inhibitor, evaluating patients as part of a 28-day treatment cycle in adult patients with acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), high-risk myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN) overlap syndrome. The study will employ a "3+3" dose escalation design. The dose may be escalated until a minimum safe and biologically effective dose or MTD is reached.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multicenter, Dose Escalation Study of PRT1419 Injection in Patients With Relapsed/Refractory Hematologic Malignancies
Actual Study Start Date : March 22, 2022
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: PRT1419
PRT1419 will be administered by intravenous infusion
 Drug: PRT1419
PRT1419 will be administered by intravenous infusion


Outcome Measures
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Primary Outcome Measures :
  1. Dose limiting toxicities (DLT) of PRT1419 [ Time Frame: Baseline through Day 28 ]
    Dose limiting toxicities will be evaluated through the first cycle

  2. Minimum safe and biologically-effective dose [ Time Frame: Baseline through approximately 1.5 years ]
    The minimum safe and biologically-effective dose will be established for further investigation in participants with advanced hematologic malignancies

  3. Recommended phase 2 dose (RP2D) and schedule of PRT1419 [ Time Frame: Baseline through approximately 1.5 years ]
    The RP2D will be established for further investigation in participants with advanced hematologic malignancies


Secondary Outcome Measures :
  1. Safety and tolerability of PRT1419: AEs, SAEs, CTCAE assessments [ Time Frame: Baseline through approximately 2 years ]
    Safety and tolerability will be assessed by recording adverse events (AEs) and serious adverse events (SAEs) according to Common Terminology Criteria for Adverse Events (CTCAE)

  2. Pharmacokinetic profile of PRT1419: maximum observed plasma concentration [ Time Frame: Baseline through approximately 2 years ]
    PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration

  3. Anti-tumor activity of PRT1419: measurement of objective responses [ Time Frame: Baseline through approximately 2 years ]
    Anti-tumor activity of PRT1419 based on the measurement of objective responses to PRT1419 according to the disease-specific response criteria for patients with hematologic malignancies


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 to 2
  • Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
  • Left ventricular ejection fraction of ≥ 50%
  • All patients must have recovered from the effects of any prior cancer related therapy, radiotherapy, or surgery (toxicity no greater than Grade 1).
  • All patients on prior investigational agents must wait at least 5 half-lives of the agent in question, or 14 days, whichever is longer before enrollment into the trial, and until any toxicities of the prior investigational agent have resolved to Grade 1 or a baseline state
  • Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use a highly effective method of contraception during the trial

  • AML patients only: Pathologically confirmed diagnosis of AML as defined by the WHO Classification and patients with targeted mutations must have been treated with appropriate therapy for their disease

    a. White blood cell count < 25 × 10^9/L. Hydroxyurea or leukapheresis are permitted to meet this criterion

  • CMML patients only: intermediate-2 or high risk per CMML-specific prognostic scoring system (CPSS) or clinical/molecular CPSS (CPSS-mol) criteria. Must have failed at least 4-6 cycles of prior therapy with a hypomethylating agent
  • High Risk MDS - MDS/MPN Overlap Syndrome: intermediate, high, or very high risk by International Prognostic Scoring System-Revised [IPSS-R] criteria that is relapsed or refractory to approved therapies, including at least 4-6 cycles of a hypomethylating agent, or MDS/MPN Overlap Syndrome (displaying both fibrosis and dysplastic features)

Exclusion Criteria:

  • Known hypersensitivity to any of the components of PRT1419
  • Female patients who are pregnant or lactating
  • Active inflammatory disorders of the gastrointestinal tract, or patients with GI malabsorption
  • Mean QTcF interval of > 480 msec
  • History of heart failure, additional risk factors for arrhythmias or requiring concomitant medications that prolong the QT/QTc interval
  • Elevated cardiac troponin or evidence of recent cardiac injury
  • HIV positive; known active hepatitis B or C
  • Hematopoietic stem-cell transplantation within the last 90 days or have GVHD Grade > 1 at study entry
  • Uncontrolled intercurrent illnesses
  • Treatment with either OATP1B1, OATP1B3 substrates or strong inhibitors of CYP2C8
  • Prior exposure to an MCL1 inhibitor

  • History of another malignancy except for:

    1. Malignancy treated with curative intent with no known active disease for > 2 years prior to study start
    2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    3. Adequately treated carcinoma in situ without evidence of disease
    4. Other concurrent low-grade malignancies (i.e., chronic lymphocytic leukemia (CLL) (Rai 0)) may be considered after consultation with Sponsor
Contacts and Locations
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Information from the National Library of Medicine

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): NCT05107856


Contacts
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Contact: Study Contact 302-644-5434 PRT1419-03IVstudy@preludetx.com

Locations
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United States, Florida
AdventHealth Bone and Marrow Transplant Center Recruiting
Orlando, Florida, United States, 32804
United States, New York
North Shore Hematology Oncology Associates. DBA New York Cancer and Blood Specialists Recruiting
Port Jefferson Station, New York, United States, 11776
United States, Ohio
Gabrail Cancer Center Research Recruiting
Canton, Ohio, United States, 44718
United States, Pennsylvania
Thomas Jefferson University, Sidney Kimmel Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Prelude Therapeutics
More Information
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Responsible Party: Prelude Therapeutics
ClinicalTrials.gov Identifier: NCT05107856    
Other Study ID Numbers: PRT1419-03
First Posted: November 4, 2021    Key Record Dates
Last Update Posted: April 8, 2022
Last Verified: March 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prelude Therapeutics:
MCL1
Additional relevant MeSH terms:
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Leukemia
Hematologic Neoplasms
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Myeloproliferative Disorders
Neoplasms by Histologic Type
 Neoplasms
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Site
Myelodysplastic-Myeloproliferative Diseases