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

NCT ID: NCT04543305

Last Updated: 2022-11-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-28
• Study Completion Date: 2022-03-21

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.

Conditions

Multiple Myeloma; Acute Myeloid Leukemia; Non Hodgkin Lymphoma; Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PRT1419

PRT1419 will be administered orally

Group Type: EXPERIMENTAL

PRT1419

Intervention Type: DRUG

PRT1419 will be administered orally

Interventions

PRT1419

PRT1419 will be administered orally

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Prelude Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Colorado Blood Cancer Institute

Denver, Colorado, United States

Florida Cancer Specialists

Lake Mary, Florida, United States

Florida Cancer Specialists

Sarasota, Florida, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

PRT1419-01

Identifier Type: -

Identifier Source: org_study_id