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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04543305
Recruitment Status : Recruiting
First Posted : September 10, 2020
Last Update Posted : October 30, 2020
Sponsor:
Information provided by (Responsible Party):
Prelude Therapeutics

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
Multiple Myeloma Acute Myeloid Leukemia Non Hodgkin Lymphoma Myelodysplastic Syndromes Drug: PRT1419 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) 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies
Actual Study Start Date : September 28, 2020
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : September 30, 2022


Arm Intervention/treatment
Experimental: PRT1419
PRT1419 will be administered orally
Drug: PRT1419
PRT1419 will be administered orally




Primary Outcome Measures :
  1. To describe dose limiting toxicities (DLT) of PRT1419 [ Time Frame: Baseline through Day 28 ]
    Dose limiting toxicities will be evaluated through the first cycle

  2. To determine the maximally tolerated dose (MTD) and/or optimal biological dose (OBD) [ Time Frame: 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

  3. To determine the recommended phase 2 dose (RP2D) and schedule of PRT1419 [ Time Frame: 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 :
  1. To describe the adverse event profile and tolerability of PRT1419 [ Time Frame: Baseline through approximately 2 years ]
    Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy

  2. To describe the pharmacokinetic profile of PRT1419 [ Time Frame: Baseline through approximately 2 years ]
    PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration

  3. To describe any anti-tumor activity of PRT1419 [ Time Frame: Baseline through approximately 2 years ]
    Anti-tumor activity of PRT1419 will be based on the measurement of objective responses



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04543305


Contacts
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Contact: Study Contact 302-644-5434 PRT1419-01Study@Preludetx.com

Locations
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United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Study Contact    302-644-5454    PRT1419-01Study@Preludetx.com   
United States, Florida
Florida Cancer Specialists Recruiting
Lake Mary, Florida, United States, 32742
Contact: Study Contact    302-644-5434    PRT1419-01Study@Preludetx.com   
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Study Contact    302-644-5434    PRT1419-01Study@Preludetx.com   
Sponsors and Collaborators
Prelude Therapeutics
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Responsible Party: Prelude Therapeutics
ClinicalTrials.gov Identifier: NCT04543305    
Other Study ID Numbers: PRT1419-01
First Posted: September 10, 2020    Key Record Dates
Last Update Posted: October 30, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Hematologic Neoplasms
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Neoplasms by Site