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

NCT04543305 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PRT1419-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 5

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• To describe dose limiting toxicities (DLT) of PRT1419

  Dose limiting toxicities will be evaluated through the first cycle

  Baseline through Day 28

• 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

  Baseline through approximately 2 years

• 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

  Baseline through approximately 2 years

Secondary Outcomes (3)

• To describe the adverse event profile and tolerability of PRT1419

  Baseline through approximately 2 years

• To describe the pharmacokinetic profile of PRT1419

  Baseline through approximately 2 years

• To describe any anti-tumor activity of PRT1419

  Baseline through approximately 2 years

Study Arms (1)

PRT1419

EXPERIMENTAL

PRT1419 will be administered orally

Drug: PRT1419

Interventions

PRT1419 DRUG

PRT1419 will be administered orally

PRT1419

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Prelude Therapeutics: lead

Study Sites (5)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Lake Mary, Florida, 32742, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Lymphoma; Lymphatic Diseases; Bone Marrow Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2020
• First Posted: September 10, 2020
• Study Start: September 28, 2020
• Primary Completion: March 21, 2022
• Study Completion: March 21, 2022
• Last Updated: November 15, 2022

Record last verified: 2022-11

Locations

US (5)