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

NCT02395601 | Completed Phase 1

• 1 other identifier: 1205-01
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 6

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.

Conditions

B-Cell Lymphoma

Keywords

B-Cell Lymphoma; EZH2 Inhibitor; Phase 1

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Frequency of adverse events

  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

Study Arms (1)

CPI-1205

EXPERIMENTAL

Drug: CPI-1205

Interventions

CPI-1205 DRUG

Small molecule inhibitor of the enzyme EZH2

CPI-1205

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Constellation Pharmaceuticals: lead

Study Sites (6)

Horizon Oncology Center

Lafayette, Indiana, 47905, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

The Ohio State University James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

(R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2015
• First Posted: March 23, 2015
• Study Start: March 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: May 18, 2022

Record last verified: 2022-05

Locations

US (6)