a phase 2 study of cpi-0610 with and without ruxolitinib in patients with myelofibrosis

Conditions: Myelofibrosis; Leukemia, Myelocytic, Acute; Myelodysplastic/Myeloproliferative Neoplasm; Myelodysplastic Syndrome (MDS); Preleukemia; Primary Myelofibrosis; Myeloproliferative Disorders; Bone Marrow Disease; Hematological Disease; Precancerous Conditions; Neoplasms; Leukemia; Neoplasms by Histologic Type; Essential Thrombocytosis

Summary: 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.

Keywords: phase 1 phase 2 oncology bet inhibitor ruxolitinib pelabresib