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

ID#: NCT02158858

Age: 18 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 1/Phase 2

Recruitment Status: Recruiting

Start Date: June 01, 2014

End Date: March 01, 2020

Contact Information:
Debbie Johnson
617-714-0555
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.
Eligibility: Inclusion Criteria

- Adult (aged ≥ 18 years)

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

- Dynamic International Prognostic Scoring System (DIPSS) risk category of intermediate-1 or higher.

- 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

- 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:

- Palpable spleen ≥ 5 cm that is below the costal margin on physical examination OR RBC transfusion dependent (defined as an average of ≥2 units of RBC transfusions per month over the 12 weeks prior to enrollment)

- 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

- Combination Arm (Arm 2): Must have received single agent ruxolitinib and be on a stable dose for a minimum 8 weeks For Arm 3 (JAK inhibitors naïve) the following criteria should be considered:

- Platelet count ≥ 100 x 10^9/L without the assistance of thrombopoietic factors or transfusions

- Palpable spleen ≥ 5 cm that is below the costal margin on physical examination

- At least 2 symptoms measurable (score ≥ 3) or a total score of ≥ 10 using the MFSAF v4.0

- No prior treatment with JAKi allowed 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.