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

Primary Purpose

Multiple Myeloma, Acute Myeloid Leukemia, Non Hodgkin Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PRT1419
Sponsored by
Prelude Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
  • Left ventricular ejection fraction of ≥50%
  • 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
  • Patients must have recovered from the effects of any prior cancer related therapy, radiotherapy or surgery (toxicity ≤ 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 study entry

  • 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

    • White blood cell count < 25 x 10^9/L. Hydrea 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 prior therapy with a hypomethylating agent.
  • MDS patients only: Intermediate, high, or very high risk by International Prognostic Scoring System-Revised [IPSS-R] criteria that is relapsed or refractory to approved therapies or MDS/MPN Overlap Syndrome (displaying both fibrosis and dysplastic features).
  • NHL patients only: Histologically or cytologically confirmed NHL, including B- and T-cell lymphomas that is relapsed or refractory or intolerant to approved therapies. Must have one lesion that can be measured for response
  • MM patients only: Measurable disease defined by one or more of the following: Serum M-protein ≥ 0.5 g/dL, Urine M-protein ≥ 200 mg/24 hours, Serum Free Light Chain (sFLC) > 10 mg/dL with normal serum FLC ratio. Presence of soft tissue plasmacytoma confirmed by imaging

  • NHL and MM patients only: must have the following lab values within 14 days prior to study Day 1:

    • ANC ≥1.0 x 10^3 μL
    • Platelet count ≥50,000 μL

Exclusion Criteria:

  • Known hypersensitivity to any of the components of PRT1419
  • Female patients who are pregnant or lactating
  • Mean QTcF interval of >480 msec
  • History of heart failure, additional risk factors for arryhthmias or requiring concomitant medications that prolong the QT/QTc interval
  • Hematopoietic stem-cell transplant < 90 days or have GVHD Grade >1 at study entry
  • Uncontrolled intercurrent illnesses
  • Treatment with strong inhibitors of CYP2C8 and/or P-glycoprotein for which there are no therapeutic substitutions
  • Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption
  • HIV positive; known active hepatitis B or C
  • Prior exposure to an MCL1 inhibitor

  • History of another malignancy except:

    • Malignancy treated with curative intent with no known active disease for >2 years at study entry
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    • Adequately treated carcinoma in situ without evidence of disease
    • Other concurrent low-grade malignancies (i.e chronic lymphocytic leukemia (Rai 0)) may be considered after consultation with Sponsor.

Sites / Locations

  • Colorado Blood Cancer Institute
  • Florida Cancer Specialists
  • Florida Cancer Specialists
  • Memorial Sloan Kettering Cancer Center
  • The University of Texas MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PRT1419

Arm Description

PRT1419 will be administered orally

Outcomes

Primary Outcome Measures

To describe dose limiting toxicities (DLT) of PRT1419
Dose limiting toxicities will be evaluated through the first cycle
To determine the maximally tolerated dose (MTD) and/or optimal biological dose (OBD)
The MTD and/or OBD will be established for further investigation in participants with multiple myeloma, Non-Hodgkin's Lymphoma, acute myeloid leukemia and myelodysplastic syndrome
To determine the recommended phase 2 dose (RP2D) and schedule of PRT1419
The RP2D will be established for further investigation in participants with multiple myeloma, Non-Hodgkin's Lymphoma, acute myeloid leukemia and myelodysplastic syndrome

Secondary Outcome Measures

To describe the adverse event profile and tolerability of PRT1419
Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy
To describe the pharmacokinetic profile of PRT1419
PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration
To describe any anti-tumor activity of PRT1419
Anti-tumor activity of PRT1419 will be based on the measurement of objective responses

Full Information

First Posted
September 2, 2020
Last Updated
November 14, 2022
Sponsor
Prelude Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT04543305
Brief Title
A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies
Official Title
A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
September 28, 2020 (Actual)
Primary Completion Date
March 21, 2022 (Actual)
Study Completion Date
March 21, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Prelude Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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 in two cohorts as part of a 28-day treatment cycle in adult patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), high-risk myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MPN) overlap syndrome. Cohort A will evaluate PRT1419 administered as monotherapy in patients with either AML, CMML and/or high-risk MDS or MDS/MPN overlap. Cohort B will evaluate PRT1419 administered as monotherapy in patients with NHL or MM. The study will employ a "3+3" dose escalation design. The dose may be escalated until a dose limiting toxicity is identified.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Acute Myeloid Leukemia, Non Hodgkin Lymphoma, Myelodysplastic Syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PRT1419
Arm Type
Experimental
Arm Description
PRT1419 will be administered orally
Intervention Type
Drug
Intervention Name(s)
PRT1419
Intervention Description
PRT1419 will be administered orally
Primary Outcome Measure Information:
Title
To describe dose limiting toxicities (DLT) of PRT1419
Description
Dose limiting toxicities will be evaluated through the first cycle
Time Frame
Baseline through Day 28
Title
To determine the maximally tolerated dose (MTD) and/or optimal biological dose (OBD)
Description
The MTD and/or OBD will be established for further investigation in participants with multiple myeloma, Non-Hodgkin's Lymphoma, acute myeloid leukemia and myelodysplastic syndrome
Time Frame
Baseline through approximately 2 years
Title
To determine the recommended phase 2 dose (RP2D) and schedule of PRT1419
Description
The RP2D will be established for further investigation in participants with multiple myeloma, Non-Hodgkin's Lymphoma, acute myeloid leukemia and myelodysplastic syndrome
Time Frame
Baseline through approximately 2 years
Secondary Outcome Measure Information:
Title
To describe the adverse event profile and tolerability of PRT1419
Description
Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy
Time Frame
Baseline through approximately 2 years
Title
To describe the pharmacokinetic profile of PRT1419
Description
PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration
Time Frame
Baseline through approximately 2 years
Title
To describe any anti-tumor activity of PRT1419
Description
Anti-tumor activity of PRT1419 will be based on the measurement of objective responses
Time Frame
Baseline through approximately 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 Adequate organ function (bone marrow, hepatic, renal, cardiovascular) Left ventricular ejection fraction of ≥50% 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 Patients must have recovered from the effects of any prior cancer related therapy, radiotherapy or surgery (toxicity ≤ 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 study entry 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 White blood cell count < 25 x 10^9/L. Hydrea 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 prior therapy with a hypomethylating agent. MDS patients only: Intermediate, high, or very high risk by International Prognostic Scoring System-Revised [IPSS-R] criteria that is relapsed or refractory to approved therapies or MDS/MPN Overlap Syndrome (displaying both fibrosis and dysplastic features). NHL patients only: Histologically or cytologically confirmed NHL, including B- and T-cell lymphomas that is relapsed or refractory or intolerant to approved therapies. Must have one lesion that can be measured for response MM patients only: Measurable disease defined by one or more of the following: Serum M-protein ≥ 0.5 g/dL, Urine M-protein ≥ 200 mg/24 hours, Serum Free Light Chain (sFLC) > 10 mg/dL with normal serum FLC ratio. Presence of soft tissue plasmacytoma confirmed by imaging NHL and MM patients only: must have the following lab values within 14 days prior to study Day 1: ANC ≥1.0 x 10^3 μL Platelet count ≥50,000 μL Exclusion Criteria: Known hypersensitivity to any of the components of PRT1419 Female patients who are pregnant or lactating Mean QTcF interval of >480 msec History of heart failure, additional risk factors for arryhthmias or requiring concomitant medications that prolong the QT/QTc interval Hematopoietic stem-cell transplant < 90 days or have GVHD Grade >1 at study entry Uncontrolled intercurrent illnesses Treatment with strong inhibitors of CYP2C8 and/or P-glycoprotein for which there are no therapeutic substitutions Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption HIV positive; known active hepatitis B or C Prior exposure to an MCL1 inhibitor History of another malignancy except: Malignancy treated with curative intent with no known active disease for >2 years at study entry Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease Other concurrent low-grade malignancies (i.e chronic lymphocytic leukemia (Rai 0)) may be considered after consultation with Sponsor.
Facility Information:
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Florida Cancer Specialists
City
Lake Mary
State/Province
Florida
ZIP/Postal Code
32742
Country
United States
Facility Name
Florida Cancer Specialists
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

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

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