A Phase 1 Study Evaluating CPI-0610 in Patients With Previously Treated Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Constellation Pharmaceuticals
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Constellation Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02157636
First received: May 28, 2014
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

Open-label, sequential dose escalation and expansion study of CPI-0610 in patients with previously treated multiple myeloma. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.


Condition Intervention Phase
Multiple Myeloma
Drug: CPI-0610
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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 Previously Treated Multiple Myeloma

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 malignant tumor cells; changes in cellular proliferation and in the extent of apoptosis [ Time Frame: Assessed during cycle 1 (first 21 days on study); and on cycle 2, day 1 ] [ Designated as safety issue: No ]
    This outcome measure is a composite measure

  • 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-myeloma activity associated with CPI-0610 treatment [ Time Frame: Assessed after every cycle of treatment; assessed up to approximately 12 months ] [ Designated as safety issue: No ]
    Anti-myeloma activity will be assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma


Estimated Enrollment: 36
Study Start Date: July 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: October 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 or cytologically confirmed diagnosis of multiple myeloma that has progressed despite at least one line of standard therapy
  • Must have measurable disease, defined by one or more of following: (i) a serum M protein > 0.5 g/dl measured by serum protein electrophoresis; (ii) urinary M protein excretion > 200 mg/24 hours; (iii) serum free light chain (FLC) measurement > 10 mg/dl, provided that the serum FLC ratio is abnormal
  • 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:

  • Current infection with HIV, Hepatitis B or Hepatitis C
  • 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) < 50%
  • 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
  • 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 myeloma, 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 the 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: NCT02157636

Locations
United States, Arizona
Mayo Clinic Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Office All Mayo Clinic Locations    507-538-7623      
Principal Investigator: Lief Bergsagel, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Noopur Raje, MD    617-724-4000      
Principal Investigator: Noopur Raje, MD         
United States, Pennsylvania
University of Pennsylvania - Perelman Center for Advanced Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Rita Bhagat, BS, RN, BSN, CCRP    215-614-0548    rita.bhagat@uphs.upenn.edu   
Principal Investigator: Dan Vogl, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Salah Nabhan    615-329-7215    Salah.Nabhan@scresearch.net   
Principal Investigator: Jesus Berdeja, MD         
Sponsors and Collaborators
Constellation Pharmaceuticals
The Leukemia and Lymphoma Society
  More Information

No publications provided

Responsible Party: Constellation Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02157636     History of Changes
Other Study ID Numbers: 0610-03
Study First Received: May 28, 2014
Last Updated: July 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Constellation Pharmaceuticals:
Phase 1
Oncology
BET Inhibitor

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 16, 2014