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

 Myelofibrosis / Posted 2 weeks ago

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.

  • 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 haemorrhage 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.
  • Study end date : December 31, 2022
  • Wales-Based Study Contact : Marc Jones
  • Principal Investigator : Steven Knapper
Contact details

University Hospital of Wales, Heath Park WayCardiff,CF14 4XW  Show Phone Number marc.jones4@wales.nhs.uk

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