Non Hodgkin Lymphoma Clinical Trial
A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies
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.
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.
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
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.
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There are 5 Locations for this study
Denver Colorado, 80218, United States
Lake Mary Florida, 32742, United States
Sarasota Florida, 34232, United States
New York New York, 10065, United States
Houston Texas, 77030, United States
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