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

• Status: Recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Constellation Pharmaceuticals
• Collaborator: The Leukemia and Lymphoma Society

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 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.