Open Actively Recruiting

A Phase 2 Study of CPI-0610 With and Without Ruxolitinib in Patients With Myelofibrosis

About

Brief 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.

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase I/II

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
18 Years
Maximum Age
N/A

Inclusion Criteria:

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

  • ANC ≥ 1 x 10^9/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 cm^3 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 10^9/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 10^9/L without the assistance of thrombopoietic factors or transfusions
  • Spleen volume ≥ 450 cm^3 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 × 10^9/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 × 10^9/L
    • Resistant or intolerant to HU

Exclusion Criteria:

  • 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.

Join this Trial

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Study Stats
Protocol No.
18-000603
Category
Hematology-Oncology
Oncology
Contact
Bruck Habtemariam
Location
  • UCLA Westwood
For Providers
NCT No.
NCT02158858
For detailed technical eligibility, visit ClinicalTrials.gov.