Clinical Trial: A Phase 1 Study Evaluating CPI-0610 in Patients With Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasms, and Myelofibrosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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, Myelodysplast

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

Detailed Summary:
Sponsor: Constellation Pharmaceuticals

Current Primary Outcome: 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: Same as current

Current Secondary Outcome:

  • 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 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 ]
    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) ]
  • Anti-leukemia, anti-myelodysplastic syndrome, anti-myelodysplastic/myeloproliferative neoplasm, and anti-myelofibrosis 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 ]
    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, MDS/MPN, and MF,


Original Secondary Outcome:

  • 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 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 ]
    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) ]
  • 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 ]
    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


Information By: Constellation Pharmaceuticals

Dates:
Date Received: June 5, 2014
Date Started: June 2014
Date Completion: January 2019
Last Updated: November 22, 2016
Last Verified: November 2016