A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PRT1419 PRT1419 will be administered orally |
Drug: PRT1419
PRT1419 will be administered orally
|
Outcome Measures
Primary Outcome Measures
- To describe dose limiting toxicities (DLT) of PRT1419 [Baseline through Day 28]
Dose limiting toxicities will be evaluated through the first cycle
- To determine the maximally tolerated dose (MTD) and/or optimal biological dose (OBD) [Baseline through approximately 2 years]
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 [Baseline through approximately 2 years]
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 [Baseline through approximately 2 years]
Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy
- To describe the pharmacokinetic profile of PRT1419 [Baseline through approximately 2 years]
PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration
- To describe any anti-tumor activity of PRT1419 [Baseline through approximately 2 years]
Anti-tumor activity of PRT1419 will be based on the measurement of objective responses
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
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Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
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Left ventricular ejection fraction of ≥50%
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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
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Patients must have recovered from the effects of any prior cancer related therapy, radiotherapy or surgery (toxicity ≤ Grade 1)
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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
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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
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White blood cell count < 25 x 10^9/L. Hydrea or leukapheresis are permitted to meet this criterion.
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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.
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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).
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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
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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
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NHL and MM patients only: must have the following lab values within 14 days prior to study Day 1:
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ANC ≥1.0 x 10^3 μL
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Platelet count ≥50,000 μL
Exclusion Criteria:
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Known hypersensitivity to any of the components of PRT1419
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Female patients who are pregnant or lactating
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Mean QTcF interval of >480 msec
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History of heart failure, additional risk factors for arryhthmias or requiring concomitant medications that prolong the QT/QTc interval
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Hematopoietic stem-cell transplant < 90 days or have GVHD Grade >1 at study entry
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Uncontrolled intercurrent illnesses
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Treatment with strong inhibitors of CYP2C8 and/or P-glycoprotein for which there are no therapeutic substitutions
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Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption
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HIV positive; known active hepatitis B or C
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Prior exposure to an MCL1 inhibitor
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History of another malignancy except:
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Malignancy treated with curative intent with no known active disease for >2 years at study entry
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Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
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Adequately treated carcinoma in situ without evidence of disease
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Other concurrent low-grade malignancies (i.e chronic lymphocytic leukemia (Rai 0)) may be considered after consultation with Sponsor.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Colorado Blood Cancer Institute | Denver | Colorado | United States | 80218 |
| 2 | Florida Cancer Specialists | Lake Mary | Florida | United States | 32742 |
| 3 | Florida Cancer Specialists | Sarasota | Florida | United States | 34232 |
| 4 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 5 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Prelude Therapeutics
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PRT1419-01