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Trial record 2 of 7 for:    CPI lymphoma

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by Constellation Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Constellation Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02395601
First received: March 10, 2015
Last updated: November 22, 2016
Last verified: November 2016
  Purpose
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.

Condition Intervention Phase
B-Cell Lymphoma
Drug: CPI-1205
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, in Patients With B-Cell Lymphomas

Resource links provided by NLM:


Further study details as provided by Constellation Pharmaceuticals:

Primary Outcome Measures:
  • Frequency of Dose-limiting toxicities (DLTs) [ Time Frame: DLTs asessed during Cycle 1 (first 28 days on study) ] [ Designated as safety issue: Yes ]
    Frequency of dose-limiting toxicities (DLTs) associated with CPI-1205 administration during the first cycle (first 28 days) of treatment


Secondary Outcome Measures:
  • Frequency of adverse events [ Time Frame: Assessed from Day 1 of Cycle 1 through 30 days after patient's last dose of study drug ] [ Designated as safety issue: Yes ]
    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

  • Pharmacokinetic parameters of CPI-1205: AUC(0-t), AUC(0-inf), AUCtau,ss, Tmax, Cmax, Ctrough, T1/2, Vd/F, CL/F [ Time Frame: Assessed during cycle 1 (first 28 days on study); and on cycle 2, day 1 ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Assessed during cycle 1 (first 28 days on study) ] [ Designated as safety issue: No ]
  • 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) [ Time Frame: Assessed during cycle 1 (first 28 days on study) ] [ Designated as safety issue: No ]
  • Disease response assessment will be performed using the 2014 Lugano Response Criteria for Hodgkin and Non-Hodgkin Lymphoma [ Time Frame: After every 2 cycles of treatment for the first 6 cycles, and after every 4 cycles thereafter ] [ Designated as safety issue: No ]

Estimated Enrollment: 41
Study Start Date: March 2015
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CPI-1205 Drug: CPI-1205
Small molecule inhibitor of the enzyme EZH2

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02395601

Contacts
Contact: Debbie Johnson 617 714 0531 debbie.johnson@constellationpharma.com

Locations
United States, Indiana
Horizon Oncology Center Recruiting
Layfayette, Indiana, United States, 47905
Contact: Ana Logsdon    765-446-5111    alogsdon@horizonbioadvance.com   
Principal Investigator: Wael Harb, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Jeremy Abramson, MD    617-724-4000    jabramson@mgh.harvard.edu   
Principal Investigator: Jeremy Abramson, MD         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Maribeth Hoenstein    402-559-5166    mahohens@unmc.edu   
Principal Investigator: Matthew Lunning, MD         
United States, New Jersey
John Theurer Cancer Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Kara Yannotti, MMH, BSN, RN    551-996-5168    kyannotti@hackensackumc.org   
Principal Investigator: Andre Goy, MD         
United States, Ohio
The Ohio State University James Cancer Hospital Recruiting
Columbus, Ohio, United States, 43210
Contact: Pamela Heeter, RN    614-293-9627      
Principal Investigator: Kami Maddocks, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Sarah Cannon Research Institute    615-339-4214    asksarah@scresearch.net   
Principal Investigator: Ian Flinn, MD, PhD         
Sponsors and Collaborators
Constellation Pharmaceuticals
Investigators
Study Director: Debbie Johnson Constellation Pharmaceuticals
  More Information

Responsible Party: Constellation Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02395601     History of Changes
Other Study ID Numbers: 1205-01 
Study First Received: March 10, 2015
Last Updated: November 22, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Constellation Pharmaceuticals:
B-Cell Lymphoma
EZH2 Inhibitor
Phase 1

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on December 02, 2016