A Study of PRT2527 as Monotherapy and in Combination With Zanubrutinib in Participants With R/R Hematologic Malignancies
Aggressive B-Cell Non-Hodgkin's Lymphoma, Aggressive B-Cell NHL, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
About this trial
This is an interventional treatment trial for Aggressive B-Cell Non-Hodgkin's Lymphoma focused on measuring Aggressive B-Cell Non-Hodgkin's Lymphoma, Aggressive B-Cell NHL, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, CDK9, CLL/SLL, Cyclin-Dependent Kinase 9, Hematologic Malignancies, Mantle Cell Lymphoma (MCL), PRT2527, Relapse/Refractory, Richter's Syndrome, T-cell Lymphoma (TCL), Zanubrutinib
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
Sites / Locations
- City of HopeRecruiting
- American Oncology Partners of Maryland, PARecruiting
- Laura and Isaac Perlmutter Cancer Center at NYU Langone HealthRecruiting
- Austin HealthRecruiting
- Alfred HealthRecruiting
- Monash HealthRecruiting
- Linear Clinical Research LtdRecruiting
- Jewish General HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
PRT2527 Monotherapy
PRT2527/Zanubrutinib Combination
PRT2527 will be administered by intravenous infusion once weekly on a 21-day treatment cycle at the dose level assigned during the dose escalation phase and at the defined RP2D dose for indication-specific cohorts during the dose confirmation phase.
PRT2527 will be administered by intravenous infusion once weekly on a 35-day treatment cycle for Cycle 1 followed by 21-day treatment for subsequent treatment cycles at the dose level assigned during the dose escalation phase and at the defined RP2D dose for indication specific cohort during the dose confirmation phase. Zanubrutinib will be administered orally as combination therapy once daily.