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

This is an interventional treatment trial for Myelofibrosis focused on measuring Phase 1, Phase 2, Oncology, BET Inhibitor, Ruxolitinib, Pelabresib Read More

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.