Clinical Trials /

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

NCT04543305

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies
  • Official Title: A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: PRT1419-01
  • NCT ID: NCT04543305

Conditions

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

Interventions

DrugSynonymsArms
PRT1419PRT1419

Purpose

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) and high-risk myelodysplastic syndrome (MDS). Cohort A will evaluate PRT1419
      administered as monotherapy in patients with either AML and/or high-risk MDS. 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.
    

Trial Arms

NameTypeDescriptionInterventions
PRT1419ExperimentalPRT1419 will be administered orally
  • PRT1419

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

          -  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

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To describe dose limiting toxicities (DLT) of PRT1419
Time Frame:Baseline through Day 28
Safety Issue:
Description:Dose limiting toxicities will be evaluated through the first cycle

Secondary Outcome Measures

Measure:To describe the adverse event profile and tolerability of PRT1419
Time Frame:Baseline through approximately 2 years
Safety Issue:
Description:Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy
Measure:To describe the pharmacokinetic profile of PRT1419
Time Frame:Baseline through approximately 2 years
Safety Issue:
Description:PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration
Measure:To describe any anti-tumor activity of PRT1419
Time Frame:Baseline through approximately 2 years
Safety Issue:
Description:Anti-tumor activity of PRT1419 will be based on the measurement of objective responses

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Prelude Therapeutics

Last Updated

September 9, 2020