A Study Evaluating CPI-1205 in Patients With B-Cell Lymphomas

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, in Patients With B-Cell Lymphomas

Conditions
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B-Cell Lymphoma

Intervention / Treatment
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* Drug: CPI-1205


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPI-1205<br> | Drug: CPI-1205<br>* Small molecule inhibitor of the enzyme EZH2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Dose-limiting toxicities (DLTs) | Frequency of dose-limiting toxicities (DLTs) associated with CPI-1205 administration during the first cycle (first 28 days) of treatment | DLTs asessed during Cycle 1 (first 28 days on study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events | 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 | Assessed from Day 1 of Cycle 1 through 30 days after patient's last dose of study drug | 
| 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 | 
| 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) | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-Cell Lymphoma, EZH2 Inhibitor, Phase 1