A Phase 1 Study Evaluating CPI-0610 in Patients With Progressive Lymphoma

• ClinicalTrials.gov Identifier: NCT01949883
• Recruitment Status: Completed
• First Posted: September 25, 2013
• Last Update Posted: September 6, 2019
• Sponsor: Constellation Pharmaceuticals
• Collaborator: The Leukemia and Lymphoma Society
• Information provided by (Responsible Party): Constellation Pharmaceuticals

Tracking Information

• First Submitted Date: September 10, 2013
• First Posted Date: September 25, 2013
• Last Update Posted Date: September 6, 2019
• Study Start Date: September 2013
• Actual Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 24, 2013): Frequency of dose-limiting toxicities (DLTs) associated with CPI-0610 administration during the first cycle (first 21 days) of treatment [ Time Frame: DLTs asessed during Cycle 1 (first 21 days on study) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 24, 2013)

• Safety and tolerability of CPI-0610 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, ECHO and ECOG score [ Time Frame: Assessed from Day 1 of Cycle 1 through 30 days after patient's last dose of study drug ]
• Pharmacokinetic parameters of CPI-0610: AUC(0-t), AUC(0-inf), AUCtau,ss, Tmax, Cmax, Ctrough, T1/2, Vd/F, CL/F [ Time Frame: Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1 ]
• Pharmacodynamic effects of CPI-0610: Changes in the expression of MYC and other genes in tumor tissue; changes in cellular proliferation and in the extent of apoptosis; changes in tumor metabolism [ Time Frame: Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1 ]
• Changes in the expression of a set of genes in peripheral blood mononuclear cells (PBMCs) that are sensitive to BET inhibition [ Time Frame: Assessed during cycle 1 (first 21 days on study) ]
• Anti-lymphoma activity associated with CPI-0610 treatment [ Time Frame: After every 2 cycles of treatment for the first 6 cycles, and after every 4 cycles thereafter; assessed up to approximately 12 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1 Study Evaluating CPI-0610 in Patients With Progressive Lymphoma
• Official Title: A Phase 1 Study of CPI-0610, a Small Molecule Inhibitor of BET (Bromodomain and Extra-terminal) Proteins, in Patients With Progressive Lymphoma
• Brief Summary: First in human, open-label, sequential dose escalation and expansion study of CPI-0610 in patients with progressive lymphoma. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma
• Intervention: Drug: CPI-0610

Study Arms

Experimental: CPI-0610

Intervention: Drug: CPI-0610

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 1, 2018): 64
• Original Estimated Enrollment (submitted: September 24, 2013): 33
• Actual Study Completion Date: February 2018
• Actual Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adults (aged ≥ 18 years)
• Histologically confirmed diagnosis of a non-Hodgkin or Hodgkin lymphoma that has progressed in spite of prior treatment, and for which additional effective standard therapy is not available
• Patients may have either measurable or non-measurable disease, but in all cases eligible patients must have disease that can be clinically evaluated for improvement or progression
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Adequate hematological, renal, hepatic, and coagulation laboratory assessments
• 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. CNS imaging and cerebrospinal fluid sampling are not mandatory in the absence of a clinical suspicion of lymphomatous involvement of the CNS.
• Current infection with HIV, Hepatitis B or Hepatitis C. Patients will have serologic testing performed during screening for HIV and Hepatitis B and C. Any serologic results suggestive of an ongoing viral infection will be further investigated as necessary to clarify the patient's status.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of CPI-0610, including any unresolved nausea, vomiting, or diarrhea that is CTCAE grade >1.

• 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
  • Serum cardiac troponin (cTn) level ≥ 99% percentile of the upper reference limit
  • QTcF > 470 msec on the screening ECG
  • Left ventricular ejection fraction (LVEF) < 40%
• Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded.)
• 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-0610
• Radioimmunotherapy (e.g., 131I-tositumomab, 90Y-ibritumomab tiuxetan) less than 6 weeks before the first dose of CPI-0610
• Treatment with an investigational small molecule less than 2 weeks before the first dose of CPI-0610. In addition, the first dose of CPI-0610 should not occur before a period equal to or greater than 5 half-lives of the small molecule investigational agent has elapsed.
• Treatment with a therapeutic antibody less than 4 weeks before the first dose of CPI-0610. A minimum 2-week period between the last treatment with a therapeutic antibody and the first dose of CPI-0610 may be permitted in patients with rapidly progressive or aggressive subtypes of lymphoma following discussion with the medical monitor.
• Treatment with medications that are known to be strong inhibitors or inducers of CYP450 enzymes.
• Treatment with medications that are known to carry a risk of Torsades de Pointes.
• Immunosuppressive treatment that cannot be discontinued both prior to study entry and for the duration of the study. Oral prednisone at a dose of 10 mg or less per day is allowed, as are other oral corticosteroids given at glucocorticoid-equivalent doses. Topical, nasal and inhaled corticosteroids are also allowed.
• 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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT01949883
• Other Study ID Numbers: 0610-01
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Constellation Pharmaceuticals
• Study Sponsor: Constellation Pharmaceuticals
• Collaborators: The Leukemia and Lymphoma Society

Investigators

• Study Director: Debbie Johnson; Constellation Pharmaceuticals

• PRS Account: Constellation Pharmaceuticals
• Verification Date: September 2019