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

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 (total of greater than 6 RBC transfusions) 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
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 Myelofibrosis Symptom Assessment Form Version 4.0 ( 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 pelabresib 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.