A Phase 1 Study Evaluating CPI-0610 in Patients With Acute Leukemia, Myelodysplastic Syndrome, or Myelodysplastic/Myeloproliferative Neoplasms

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Constellation Pharmaceuticals
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Constellation Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02158858
First received: June 5, 2014
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

Open-label, sequential dose escalation and expansion study of CPI-0610 in patients with previously treated Acute Leukemia, Myelodysplastic Syndrome, or Myelodysplastic/Myeloproliferative Neoplasms. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.


Condition Intervention Phase
Acute Leukemia (AML)
Myelodysplastic Syndrome (MDS)
Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN)
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 Acute Leukemia, Myelodysplastic Syndrome, or Myelodysplastic/Myeloproliferative Neoplasms

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 leukemic 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 is a composite outcome 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-leukemia, anti-myelodysplastic syndrome, or anti-myelodysplastic/myeloproliferative neoplasm activity associated with CPI-0610 treatment [ Time Frame: Assessed 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 ]
    Leukemia, MDS and MDS/MPN will be assessed using the 2013 NCCN criteria for ALL, the 2003 Cheson criteria for AML, and the 2006 modified International Working Group (IWG) criteria for MDS and MDS/MPN


Estimated Enrollment: 36
Study Start Date: June 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:

  • Adult (aged ≥ 18 years)
  • Histologically or cytologically confirmed diagnosis of one of the following hematologic malignancies: AML, ALL, acute undifferentiated or biphenotypic leukemia, CML in blast crisis, MDS or MDS/MPN
  • ECOG performance status ≤2.
  • Adequate hematological, renal, hepatic, and coagulation laboratory assessments
  • Patients must give written informed consent to participate in this study before the performance of any study-related procedure.

Exclusion Criteria:

  • Newly diagnosed acute leukemia that has not been treated with a standard induction chemotherapeutic regimen or with another anti-leukemic agent
  • Relapsed or refractory acute leukemia, where additional induction chemotherapy is considered to be of potential clinical benefit
  • Acute leukemia in relapse less than 6 months following allogeneic stem cell transplantation
  • CML in blast crisis and previously treated with only one bcr-abl TKI
  • Very low or low risk MDS without previous treatment
  • Central nervous system (CNS) (e.g., leptomeningeal) involvement by leukemia
  • 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 with a small molecule therapeutic other than hydroxyurea or radiotherapy less than 2 weeks before the first dose of CPI-0610
  • Administration of 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 disease, following discussion with the medical monitor
  • 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 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: NCT02158858

Locations
United States, Indiana
Horizon Oncology Center Recruiting
Layfayette, Indiana, United States, 47905
Contact: Wael Harb, MD    765-446-5111    info@horizonbioadvance.com   
Principal Investigator: Wael Harb, MD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Amir Fathi, MD    617-724-1124    afathi@partners.org   
Principal Investigator: Amir Fathi, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Eytan Stein, MD    212-639-3314      
Principal Investigator: Eytan Stein, MD         
United States, Pennsylvania
University of Pennsylvania - Perelman Center for Advanced Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Jessica McGraw    215-662-4610    Jessica.Mcgraw@uphs.upenn.edu   
Principal Investigator: James Mangan, MD         
Sponsors and Collaborators
Constellation Pharmaceuticals
The Leukemia and Lymphoma Society
  More Information

No publications provided

Responsible Party: Constellation Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02158858     History of Changes
Other Study ID Numbers: 0610-02
Study First Received: June 5, 2014
Last Updated: September 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Constellation Pharmaceuticals:
Phase 1
Oncology
BET Inhibitor

Additional relevant MeSH terms:
Neoplasms
Myelodysplastic Syndromes
Preleukemia
Leukemia
Syndrome
Acute Disease
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms by Histologic Type
Disease
Pathologic Processes
Disease Attributes

ClinicalTrials.gov processed this record on September 18, 2014