Non Hodgkin Lymphoma Clinical Trial
A Study of PRT2527 as Monotherapy and in Combination With Zanubrutinib in Participants With R/R Hematologic Malignancies
Summary
This is a Phase 1 dose-escalation study of PRT2527, a potent and highly selective cyclin-dependent kinase (CDK) 9 inhibitor, in participants with select relapsed or refractory (R/R) hematologic malignancies. The purpose of this study is to evaluate the safety, tolerability, recommended phase 2 dose (PR2D), and preliminary efficacy of PRT2527.
Full Description
This is an open-label, multi-center, dose-escalation, Phase 1 study of PRT2527, a CDK9 inhibitor, as monotherapy and in combination with zanubrutinib, a Bruton tyrosine kinase inhibitor (BTKi), evaluating participants with select R/R hematologic malignancies including aggressive B-cell lymphoma subtypes, mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), including Richter's syndrome and T-cell lymphoma (TCL) subtypes. The study will be conducted in two parts, the dose escalation phase and the dose confirmation phase for both monotherapy and combination therapy. The dose escalation phase will evaluate escalating doses of PRT2527 as a monotherapy and in combination with zanubrutinib until MTD is identified or when the RP2D is determined. The dose confirmation phase will evaluate indication-specific cohorts at the RP2D to confirm the dose. Approximately 104 participants will be enrolled in the dose escalation and indication-specific, dose confirmation cohorts.
Eligibility Criteria
Inclusion Criteria:
Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
Histologically or cytologically confirmed diagnosis of aggressive B-cell lymphoma subtypes, MCL, CLL/SLL, including Richter's syndrome, based on local testing , or TCL (monotherapy only) that have relapsed or become refractory to or be ineligible for standard-of-care therapy
Must provide either an archival or fresh tumor tissue sample from a core or excisional/surgical biopsy
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Adequate organ function (hematology, renal, and hepatic)
Echocardiogram (or multigated acquisition [MUGA] scan) indicating a left ventricular ejection fraction of ≥ 50%
Exclusion Criteria:
Have active central nervous system involvement by malignancy, uncontrolled intercurrent illnesses, and active infections requiring systemic therapy
Have undergone HSCT within the last 90 days or have graft versus host disease (GvHD) Grade > 1 at study entry
Mean corrected QT interval of > 470 msec following triplicate ECG measurements or a history of long QT Syndrome
Have severe pulmonary disease with hypoxemia
History of another malignancy except for adequately treated non-melanoma skin cancer or lentigo maligna, superficial bladder cancer, and carcinoma in situ of the cervix without evidence of disease, and asymptomatic prostate cancer without known metastatic disease and no requirement for therapy
Concurrent treatment or within 15 days of starting study treatment with strong CYP3A4 inhibitors or inducers or use of moderate CYP3A4 inducers (for combination therapy only)
Prior exposure to a CDK9 inhibitor
Wait at least 5 half-lives of the agent or 14 days after their investigational or approved therapies before start of study treatment, whichever is shorter
Mean corrected QT interval of > 470 msec following triplicate ECG measurement or history of long QT syndrome
T-Cell leukemias
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 23 Locations for this study
Duarte California, 91010, United States
La Jolla California, 92037, United States
Bethesda Maryland, 20817, United States
Boston Massachusetts, 02215, United States
New York New York, 10016, United States
Charlottesville Virginia, 22903, United States
Heidelberg Victoria, 3084, Australia
Melbourne Victoria, 3004, Australia
Melbourne Victoria, 3168, Australia
Perth Western Australia, 6009, Australia
Montreal Quebec, H3T 1, Canada
Creteil , 94010, France
Lille , 59000, France
Lyon , 69373, France
Saint-Cloud , 92210, France
Koln North Rhine-Westphalia, 50937, Germany
Meldola FC, 47014, Italy
Ravenna , 48121, Italy
Busan , 47392, Korea, Republic of
Daegu , 42601, Korea, Republic of
Seoul , 06351, Korea, Republic of
Kraków Malopolskie, 30-72, Poland
Bellinzona Ticino, 6500, Switzerland
How clear is this clinincal trial information?