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

B-Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02395601
• Other study ID #: 1205-01
• Status: Completed
• Phase: Phase 1
• Start date: March 2015
• Est. completion date: December 2018

Study information

• Verified date: May 2022
• Source: Constellation Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell

Intervention

Drug:
• CPI-1205
Small molecule inhibitor of the enzyme EZH2

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Ohio State University James Cancer Hospital	Columbus	Ohio
United States	John Theurer Cancer Center	Hackensack	New Jersey
United States	Horizon Oncology Center	Lafayette	Indiana
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	University of Nebraska Medical Center	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Constellation Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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