A Study Evaluating CPI-1205 in Patients With B-Cell Lymphomas
- Registration Number
- NCT02395601
- Lead Sponsor
- Constellation Pharmaceuticals
- Brief Summary
First in human, open-label, sequential dose escalation and expansion study of CPI-1205 in patients with progressive B-cell lymphomas. CPI-1205 is a small molecule inhibitor of EZH2.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 41
Adults (aged ≥ 18 years)
Histologically confirmed diagnosis of a B-cell lymphoma that has progressed in spite of prior treatment, and for which additional effective standard therapy is not available
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Adequate hematological, renal, hepatic, and coagulation laboratory assessments
Must give written informed consent to participate in this study before the performance of any study-related procedure
A primary lymphoma of the central nervous system (CNS) or known lymphomatous involvement of the CNS
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of CPI-1205, including any unresolved nausea, vomiting, or diarrhea that is CTCAE grade >1
Treatment with proton pump inhibitors, H2 antagonists, or antacids
Achlorhydria, either documented or suspected on the basis of an associated disease (e.g., pernicious anemia, atrophic gastritis, or certain gastric surgical procedures)
Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- Acute myocardial infarction or angina pectoris ≤ 6 months prior to starting study drug
- New York Heart Association Class III or IV congestive heart failure
- QTcF > 470 msec on the screening ECG
Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded)
A past medical history of other clinically significant cardiovascular disease (e.g., uncontrolled hypertension, history of labile hypertension or history of poor compliance with an antihypertensive regimen)
Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (e.g., clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection)
Systemic anti-cancer treatment or radiotherapy less than 2 weeks before the first dose of CPI 1205
Radioimmunotherapy (e.g., 131I-tositumomab, 90Y-ibritumomab tiuxetan) less than 6 weeks before the first dose of CPI-1205
Treatment with an investigational small molecule less than 2 weeks before the first dose of CPI-1205.
Treatment with a therapeutic antibody less than 4 weeks before the first dose of CPI-1205.
Treatment with medications that are strong inhibitors of CYP3A4
Treatment with medications that are inducers of CYP3A4 enzymes
Treatment with medications that are known to carry a risk of Torsades de Pointes
Pregnant or lactating women
Women of child bearing potential and men with reproductive potential, if they are unwilling to use adequate contraception while on study therapy and for 3 months thereafter
Patients unwilling or unable to comply with this study protocol
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CPI-1205 CPI-1205 -
- Primary Outcome Measures
Name Time Method Frequency of Dose-limiting toxicities (DLTs) DLTs asessed during Cycle 1 (first 28 days on study) Frequency of dose-limiting toxicities (DLTs) associated with CPI-1205 administration during the first cycle (first 28 days) of treatment
- Secondary Outcome Measures
Name Time Method Pharmacokinetic parameters of CPI-1205: AUC(0-t), AUC(0-inf), AUCtau,ss, Tmax, Cmax, Ctrough, T1/2, Vd/F, CL/F Assessed during cycle 1 (first 28 days on study); and on cycle 2, day 1 Frequency of adverse events Assessed from Day 1 of Cycle 1 through 30 days after patient's last dose of study drug Safety and tolerability of CPI-1205 as assessed by: frequency of adverse events and serious adverse events; changes in hematology and clinical chemistry values; changes in physical examination, vital signs, electrocardiogram, and ECOG score
Disease response assessment will be performed using the 2014 Lugano Response Criteria for Hodgkin and Non-Hodgkin Lymphoma After every 2 cycles of treatment for the first 6 cycles, and after every 4 cycles thereafter Pharmacodynamic effects of CPI-1205 in lymphoma tissue: changes in levels of the trimethylated form of lysine residue 27 on histone 3; changes in the expression of genes whose transcription may be altered by EZH2 inhibition Assessed during cycle 1 (first 28 days on study) Pharmacodynamic effects of CPI-1205 in bone marrow and in skin: changes in global levels of the trimethylated form of lysine residue 27 on histone 3 (H3K27me3) Assessed during cycle 1 (first 28 days on study)
Trial Locations
- Locations (6)
John Theurer Cancer Center
🇺🇸Hackensack, New Jersey, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Horizon Oncology Center
🇺🇸Lafayette, Indiana, United States
The Ohio State University James Cancer Hospital
🇺🇸Columbus, Ohio, United States