A Study of PRT2527 as Monotherapy and in Combination With Zanubrutinib or Venetoclax in Participants With R/R Hematologic Malignancies

Phase 1

Recruiting

• Conditions: Aggressive B-Cell Non-Hodgkin's Lymphoma (NHL); Diffuse Large B-cell Lymphoma (DLBCL); Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL); Mantle Cell Lymphoma (MCL); Richter's Syndrome; T-cell Lymphoma; Marginal Zone Lymphoma; Myeloid Malignancies; Acute Myeloid Leukemia (AML); Chronic Myelomonocytic Leukemia (CMML)

• Registration Number: NCT05665530
• Lead Sponsor: Prelude Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-12-16
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria:<br><br> - Willing and able to comply with all scheduled visits, treatment plan, laboratory<br> tests, lifestyle considerations, and other study procedures<br><br> - Histologically or cytologically confirmed diagnosis of aggressive B-cell lymphoma<br> subtypes, MCL, MZL, or CLL/SLL (including Richter's syndrome) based on local<br> testing, or TCL (monotherapy only), AML, CMML, MDS, or MDS/MPN overlap syndrome that<br> have relapsed or become refractory to or be ineligible for standard-of-care therapy<br><br> - Eastern Cooperative Oncology Group (ECOG) Performance Status of < 2.<br><br> - Adequate organ function (hematology, renal, and hepatic)<br><br> - Echocardiogram (or multigated acquisition [MUGA] scan) indicating a left ventricular<br> ejection fraction of = 50%<br><br>Exclusion Criteria:<br><br> - Have active central nervous system involvement by malignancy, uncontrolled<br> intercurrent illnesses, and active infections requiring systemic therapy<br><br> - Have undergone HSCT within the last 90 days or have graft versus host disease (GvHD)<br> Grade > 1 at study entry<br><br> - Have severe pulmonary disease with hypoxemia<br><br> - History of another malignancy except for adequately treated non-melanoma skin cancer<br> or lentigo maligna, superficial bladder cancer, and carcinoma in situ of the cervix<br> without evidence of disease, and asymptomatic prostate cancer without known<br> metastatic disease and no requirement for therapy<br><br> - Concurrent treatment or within 15 days of starting study treatment with strong<br> CYP3A4 inhibitors<br><br> - Prior exposure to a CDK9 inhibitor<br><br> - Wait at least 5 half-lives of the agent or 14 days after their investigational or<br> approved therapies before start of study treatment, whichever is shorter<br><br> - Mean corrected QT interval of > 470 msec following triplicate ECG measurement or<br> history of long QT syndrome<br><br> - T-Cell leukemias

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Dose limiting toxicity (DLT) of PRT2527;Safety and tolerability of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: AEs, CTCAE Assessments;Maximum tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax

Secondary Outcome Measures

Name	Time	Method
Anti-tumor activity of PRT2527 as monotherapy and in combination with zanubrutinib or venetoclax: Objective response rate (ORR);Anti-tumor activity of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: Duration of response/Complete Response (DOR/DoCR);Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: Maximum observed plasma concentration;Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: Area under the curve;Pharmacokinetic profile of PRT2527 monotherapy and in combination with zanubrutinib or venetoclax: Time of maximum concentration