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

Prelude Therapeutics (Industry)
Overall Status
CT.gov ID

Study Details

Study Description

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.

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

Study Type:
Anticipated Enrollment :
30 participants
Intervention Model:
Sequential Assignment
None (Open Label)
Primary Purpose:
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 :
Mar 22, 2022
Anticipated Primary Completion Date :
Sep 1, 2023
Anticipated Study Completion Date :
Mar 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: PRT1419

PRT1419 will be administered by intravenous infusion

Drug: PRT1419
PRT1419 will be administered by intravenous infusion

Outcome Measures

Primary Outcome Measures

  1. Dose limiting toxicities (DLT) of PRT1419 [Baseline through Day 28]

    Dose limiting toxicities will be evaluated through the first cycle

  2. Minimum safe and biologically-effective dose [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 [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 [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 [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 [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


Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Accepts Healthy Volunteers:
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

  1. 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


Site City State Country Postal Code
1 Mid Florida Hematology and Oncology Center Orange City Florida United States 32763
2 AdventHealth Bone and Marrow Transplant Center Orlando Florida United States 32804
3 New Jersey Center for Cancer Research Brick New Jersey United States 08724
4 North Shore Hematology Oncology Associates. DBA New York Cancer and Blood Specialists Port Jefferson Station New York United States 11776
5 Gabrail Cancer Center Research Canton Ohio United States 44718
6 Thomas Jefferson University, Sidney Kimmel Cancer Center Philadelphia Pennsylvania United States 19107
7 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030

Sponsors and Collaborators

  • Prelude Therapeutics


None specified.

Study Documents (Full-Text)

None provided.

More Information


None provided.
Responsible Party:
Prelude Therapeutics
ClinicalTrials.gov Identifier:
Other Study ID Numbers:
  • PRT1419-03
First Posted:
Nov 4, 2021
Last Update Posted:
Jul 14, 2022
Last Verified:
Jul 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Studies a U.S. FDA-regulated Device Product:
Keywords provided by Prelude Therapeutics
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 14, 2022