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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02395601
Recruitment Status : Completed
First Posted : March 23, 2015
Last Update Posted : September 6, 2019
Sponsor:
Information provided by (Responsible Party):
Constellation Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE March 10, 2015
First Posted Date  ICMJE March 23, 2015
Last Update Posted Date September 6, 2019
Study Start Date  ICMJE March 2015
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2015)
Frequency of Dose-limiting toxicities (DLTs) [ Time Frame: 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2015)
  • Frequency of adverse events [ Time Frame: 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
  • 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 ]
  • 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) ]
  • 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) ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating CPI-1205 in Patients With B-Cell Lymphomas
Official Title  ICMJE A Phase 1 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, in Patients With B-Cell Lymphomas
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE B-Cell Lymphoma
Intervention  ICMJE Drug: CPI-1205
Small molecule inhibitor of the enzyme EZH2
Study Arms  ICMJE Experimental: CPI-1205
Intervention: Drug: CPI-1205
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: March 20, 2015)
41
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2018
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02395601
Other Study ID Numbers  ICMJE 1205-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Constellation Pharmaceuticals
Study Sponsor  ICMJE Constellation Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Debbie Johnson Constellation Pharmaceuticals
PRS Account Constellation Pharmaceuticals
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP