Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
estimated completion
Principal Investigator
by Gary Schiller, MD (ucla)

Description

Summary

Phase 1 Part (Complete): Open-label, sequential dose escalation study of CPI-0610 in patients with previously treated Acute Leukemia, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasms, and Myelofibrosis. Phase 2 Part: Open-label study of CPI-0610 with and without Ruxolitinib in patients with Myelofibrosis. CPI-0610 is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.

Official Title

A Phase 1/2 Study of CPI-0610, a Small Molecule Inhibitor of BET Proteins: Phase 1 (in Patients With Hematological Malignancies) and Phase 2 (Dose Expansion of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis)

Keywords

Myelofibrosis Leukemia, Myelocytic, Acute Myelodysplastic/Myeloproliferative Neoplasm Myelodysplastic Syndrome (MDS) Preleukemia Primary Myelofibrosis Myeloproliferative Disorders Bone Marrow Disease Hematological Disease Precancerous Conditions Neoplasms Leukemia Neoplasms by Histologic Type Essential Thrombocytosis Phase 1 Phase 2 Oncology BET Inhibitor Ruxolitinib Pelabresib Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Myelodysplastic-Myeloproliferative Diseases Hematologic Diseases Bone Marrow Diseases Thrombocytosis Thrombocythemia, Essential CPI-0610

Eligibility

You can join if…

Open to people ages 18 years and up

Phase 2 part: Patients with confirmed diagnosis of MF who meet all of the following criteria:

  • ANC ≥ 1 x 109/L without the assistance of granulocyte growth factors

  • Peripheral blood blast count <10%
  • ECOG performance status ≤ 2.
  • Adequate hematological, renal, hepatic, and coagulation laboratory assessments
  • No prior treatment with a BET inhibitor
  • Patients must give written informed consent to participate in this study before the performance of any study-related procedure.

For Arm 1 and 2 the following criteria should be considered:

  • Patients with confirmed diagnosis of MF who meet all of the following criteria
  • Dynamic International Prognostic Scoring System (DIPSS) risk category of intermediate-2 or higher
  • Spleen volume ≥ 450 cm3 by MRI or CT for Cohorts 1B and 2B OR RBC transfusion dependent (defined as an average of ≥2 units of RBC transfusions per month over the 12 weeks prior to enrollment for Cohorts 1A and 2A)

  • At least 2 symptoms measurable (Score ≥ 1) using the Myelofibrosis Symptom Assessment Form Version 4.0 (MFSAF v4.0)
  • Platelet count ≥ 75 x 109/L without the assistance of thrombopoietic factors or transfusions for at least 14 days

Monotherapy Arm (Arm 1): Previously treated with a JAK inhibitor and be intolerant, resistant, refractory, or lost response to the JAK inhibitor; have not received the JAK inhibitor within 2 weeks prior to the start of study drug, or are ineligible to be treated with a JAK inhibitor

Combination Arm (Arm 2): Must have received single agent ruxolitinib and be on a stable dose for a minimum 8 weeks but have disease that is not being adequately controlled by ruxolitinib

For Arm 3 (JAK inhibitors naïve) the following criteria should be considered:

  • Patients with confirmed diagnosis of MF who meet all of the following criteria
  • Dynamic International Prognostic Scoring System (DIPSS) risk category of intermediate-2 or higher
  • Platelet count ≥ 100 x 109/L without the assistance of thrombopoietic factors or transfusions

  • Spleen volume ≥ 450 cm3 by MRI/CT

  • At least 2 symptoms measurable (Score ≥ 3) or a total score of ≥ 10 using the MFSAF v4.0
  • No prior treatment with JAKi allowed

For Arm 4 (ET Expansion) the following criteria should be considered:

  • Patients with a confirmed diagnosis of ET
  • High-risk disease, defined as meeting at least one of the following criteria:
  • Age > 60 years
  • Platelet count > 1500 × 109/L (at any point during the patient's disease)

  • Previously documented thrombosis, erythromelalgia, or migraine
  • Previous hemorrhage related to ET
  • Diabetes or hypertension requiring pharmacological therapy for > 6 months
  • Have ≥2 symptoms with an average score ≥ 3 over the 7-day period prior to Cycle 1 Day 1 or an average total score of ≥15 over the 7-day period prior to Cycle 1 Day 1 using the using the MPN SAF
  • Platelets > 600 × 109/L

  • Resistant or intolerant to HU

You CAN'T join if...

  • Current known active or chronic infection with human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C.
  • Impaired cardiac function or clinically significant cardiac diseases
  • Patients with Child-Pugh Class B or C
  • Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of CPI-0610 and/or ruxolitinib, including any unresolved nausea, vomiting, or diarrhea that is CTCAE Grade >1
  • Prior treatment with a BET inhibitor.
  • Pregnant or lactating women
  • Any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study
  • Patients unwilling or unable to comply with this study protocol.

Locations

  • UCLA Medical Center accepting new patients
    Los Angeles California 90095 United States
  • Mayo Clinic - Research Center accepting new patients
    Phoenix Arizona 85054 United States

Lead Scientist at University of California Health

  • Gary Schiller, MD (ucla)
    Professor-in-Residence, Medicine. Authored (or co-authored) 77 research publications.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Constellation Pharmaceuticals
ID
NCT02158858
Phase
Phase 1/2
Study Type
Interventional
Last Updated