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A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies

Primary Purpose

Relapsed/Refractory Advanced Solid Tumors, Relapsed/Refractory Diffuse Large B-cell Lymphoma, Relapsed/Refractory Myelodysplasia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PRT543
Sponsored by
Prelude Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/Refractory Advanced Solid Tumors focused on measuring PRMT5, PRMT5 Inhibitor

Eligibility Criteria

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

Inclusion Criteria:

  • Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome, acute myeloid leukemia or chronic myelomonocytic leukemia; or relapsed myelofibrosis. All malignancies must be refractory to established therapies
  • Biomarker-selected solid tumors
  • Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
  • Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
  • Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use an effective method of contraception during the trial

Exclusion Criteria:

  • Primary malignancies of the Central Nervous System(CNS) or uncontrolled CNS metastases
  • Requirement of pharmacologic doses of glucocorticoids
  • Prior treatment with chimeric antigen receptor T cells (CAR-T cells)
  • HIV positive; known active hepatitis B or C
  • Known hypersensitivity to any of the components of PRT543
  • Prior allogeneic bone marrow transplant; autologous hematopoietic transplantation less than 100 days since transplantation

Sites / Locations

  • Banner MD Anderson Cancer Center
  • UCSF Precision Cancer Medicine Building
  • Christiana Care Health Services, Christiana Hospital
  • Florida Cancer Specialists
  • Florida Cancer Specialist
  • Moffitt Cancer Center
  • Georgia Cancer Center at Augusta University
  • University of Iowa Hospitals and Clinics
  • Norton Cancer Institute, St. Matthews Campus
  • Ochsner Clinic Foundation
  • Dana Farber Cancer Institute
  • University of Michigan
  • Atlantic Health System / Morristown Medical Center
  • Montefiore Medical Center
  • Memorial Sloan Kettering Cancer Center
  • Levine Cancer Institute
  • The Ohio State University and Wexner Medical Center
  • Thomas Jefferson University Hospital
  • UPMC Hillman Cancer Center
  • PLLC
  • The University of Texas MD Anderson Cancer Center
  • MD Anderson Cancer Center
  • Seattle Cancer Care Alliance

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PRT543

Arm Description

PRT543 will be administered orally

Outcomes

Primary Outcome Measures

To describe dose limiting toxicities (DLT) of PRT543
Dose limiting toxicities (DLTs) will be evaluated during the first cycle
To determine the maximally tolerated dose (MTD)
The maximum tolerated dose (MTD) will be established for further investigation in participants with advanced malignancies who have failed prior treatments.
To determine the recommended phase 2 dose (RP2D) and schedule of PRT543
The recommended phase 2 dose (RP2D) and optimal dosing schedule of PRT543 will be established for further investigation in participants with advanced malignancies who have failed prior treatments.

Secondary Outcome Measures

To describe the adverse event profile and tolerability of PRT543
Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy
To determine the maximum observed plasma concentration (Cmax) of PRT543
PRT543 pharmacokinetics will be calculated including the maximum observed plasma concentration.
To determine the time to reach maximum observed plasma concentration (Tmax) of PRT543
PRT543 pharmacokinetics will be calculated including the time to reach maximum observed plasma concentration

Full Information

First Posted
March 8, 2019
Last Updated
March 24, 2023
Sponsor
Prelude Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT03886831
Brief Title
A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies
Official Title
A Phase 1, Open-Label, Multicenter, Dose Escalation, Dose Expansion Study of PRT543 in Patients With Advanced Solid Tumors and Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
February 11, 2019 (Actual)
Primary Completion Date
November 16, 2022 (Actual)
Study Completion Date
November 16, 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
No

5. Study Description

Brief Summary
This is a Phase 1 cohort, dose-escalation, dose-expansion study of PRT543 in patients with advanced cancers who have exhausted available treatment options. The purpose of this study is to define a safe dose and schedule to be used in subsequent development of PRT543.
Detailed Description
This is a multicenter, open-label, sequential-cohort, dose-escalation, dose-expansion Phase 1 study of PRT543 in patients with advanced cancers who have exhausted available treatment options. Enrollment will take place concurrently into two distinct patient groups (one for solid tumors/lymphomas and one for hematological malignancies). The study will consist of 2 parts, a dose escalation part, and once the recommended phase 2 dose (RP2D) has been determined, a cohort expansion part involving up to ten separate cohorts. For patients, the study will include a screening phase, a treatment phase, and a post treatment follow-up phase. An end-of-study visit will be conducted within 30 days after the last dose of PRT543.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory Advanced Solid Tumors, Relapsed/Refractory Diffuse Large B-cell Lymphoma, Relapsed/Refractory Myelodysplasia, Relapsed/Refractory Myelofibrosis, Adenoid Cystic Carcinoma, Relapsed/Refractory Mantle Cell Lymphoma, Relapsed/Refractory Acute Myeloid Leukemia, Refractory Chronic Myelomonocytic Leukemia
Keywords
PRMT5, PRMT5 Inhibitor

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
PRT543
Arm Type
Experimental
Arm Description
PRT543 will be administered orally
Intervention Type
Drug
Intervention Name(s)
PRT543
Intervention Description
PRT543 will be administered orally
Primary Outcome Measure Information:
Title
To describe dose limiting toxicities (DLT) of PRT543
Description
Dose limiting toxicities (DLTs) will be evaluated during the first cycle
Time Frame
Baseline through Day 28.
Title
To determine the maximally tolerated dose (MTD)
Description
The maximum tolerated dose (MTD) will be established for further investigation in participants with advanced malignancies who have failed prior treatments.
Time Frame
Baseline through approximately 2 years.
Title
To determine the recommended phase 2 dose (RP2D) and schedule of PRT543
Description
The recommended phase 2 dose (RP2D) and optimal dosing schedule of PRT543 will be established for further investigation in participants with advanced malignancies who have failed prior treatments.
Time Frame
Baseline through approximately 2 years.
Secondary Outcome Measure Information:
Title
To describe the adverse event profile and tolerability of PRT543
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 determine the maximum observed plasma concentration (Cmax) of PRT543
Description
PRT543 pharmacokinetics will be calculated including the maximum observed plasma concentration.
Time Frame
Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.
Title
To determine the time to reach maximum observed plasma concentration (Tmax) of PRT543
Description
PRT543 pharmacokinetics will be calculated including the time to reach maximum observed plasma concentration
Time Frame
Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose and 0.5, 1, 2, 4, 8, 24 hours postdose; predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.
Other Pre-specified Outcome Measures:
Title
To determine the terminal elimination half-life (t1/2) of PRT543.
Description
PRT543 pharmacokinetics will be calculated including the terminal elimination half life
Time Frame
Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.
Title
To determine the area under the plasma concentration versus time curve (AUC) of PRT543
Description
PRT543 pharmacokinetics will be calculated including area under the plasma concentration versus time curve.
Time Frame
Cycle 1 (each cycle is 28 days) on Days 1, 15, and/or 25: predose on Cycle 1, Days 3, 4, 8, 11, and/or 22. Subsequently for Cycle 2 and beyond (until end of study treatment) on Day 1.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome, acute myeloid leukemia or chronic myelomonocytic leukemia; or relapsed myelofibrosis. All malignancies must be refractory to established therapies Biomarker-selected solid tumors Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1 Adequate organ function (bone marrow, hepatic, renal, cardiovascular) Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use an effective method of contraception during the trial Exclusion Criteria: Primary malignancies of the Central Nervous System(CNS) or uncontrolled CNS metastases Requirement of pharmacologic doses of glucocorticoids Prior treatment with chimeric antigen receptor T cells (CAR-T cells) HIV positive; known active hepatitis B or C Known hypersensitivity to any of the components of PRT543 Prior allogeneic bone marrow transplant; autologous hematopoietic transplantation less than 100 days since transplantation
Facility Information:
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
UCSF Precision Cancer Medicine Building
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Christiana Care Health Services, Christiana Hospital
City
Newark
State/Province
Delaware
ZIP/Postal Code
19718
Country
United States
Facility Name
Florida Cancer Specialists
City
Lake Mary
State/Province
Florida
ZIP/Postal Code
32746
Country
United States
Facility Name
Florida Cancer Specialist
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Georgia Cancer Center at Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Norton Cancer Institute, St. Matthews Campus
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Atlantic Health System / Morristown Medical Center
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
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
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
The Ohio State University and Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
UPMC Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

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A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies

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