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

Phase 1 Part (Complete): Open-label, sequential dose escalation study of pelabresib 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.


Eligibility Criteria:
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.