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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Constellation Pharmaceuticals
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Constellation Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01949883
First received: September 10, 2013
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: CPI-0610
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-0610, a Small Molecule Inhibitor of BET (Bromodomain and Extra-terminal) Proteins, in Patients With Progressive Lymphoma

Resource links provided by NLM:


Further study details as provided by Constellation Pharmaceuticals:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: September 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CPI-0610 Drug: CPI-0610

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01949883

Locations
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Juli Murphy    720-754-4890      
Principal Investigator: Michael B Maris, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Jeremy Abramson, MD    617-724-4000      
Principal Investigator: Jeremy Abramson, MD         
United States, New Jersey
John Theurer Cancer Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Leah Cappadona    551-996-5078      
Principal Investigator: Andre Goy, MD         
United States, New York
Memorial Sloan Ketttering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Amy Copeland, RN, MSN, CNS    212-639-6104      
Principal Investigator: Anas Younes, MD         
United States, Ohio
The Ohio State University James Cancer Hospital Recruiting
Columbus, Ohio, United States, 43210
Contact: Kristie Blum, MD    614-293-7807      
Principal Investigator: Kristie Blum, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Sarah Cannon Research Institute    877-691-7274      
Principal Investigator: Ian Flinn, MD, PhD         
Sponsors and Collaborators
Constellation Pharmaceuticals
The Leukemia and Lymphoma Society
  More Information

No publications provided

Responsible Party: Constellation Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01949883     History of Changes
Other Study ID Numbers: 0610-01
Study First Received: September 10, 2013
Last Updated: March 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Constellation Pharmaceuticals:
Phase 1
Oncology
BET Inhibitor

Additional relevant MeSH terms:
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 20, 2014