Health Condition 1: C969- Malignant neoplasm of lymphoid, hematopoietic and related tissue, unspecified
Conditions
Interventions
Intervention1: Pelabresib: 125 mg tablet to be taken orally once a day on days 1 to 14 of a 21 day cycle
Intervention2: Placebo: 125 mg tablet to be taken orally once a day on days 1 to 14 of a 21 day
Sponsors
Novartis Healthcare Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Participants with a diagnosis of primary myelofibrosis (PMF) or post polycythemia vera MF or post-essential thrombocythemia MF (Post-PV/ET MF) according to the International Consensus Classification (ICC) of Myeloid Neoplasms and Acute Leukemias 2022. Participants with a spleen volume should be greater than or equal to 450 cm3 by MRI or CT scan Participants with a platelet count should be greater than or equal to 100 multiplied by 109 per L in the absence of growth factor support (including thrombopoietin mimetics/ agonists) or platelet transfusions for the previous 4 weeks. Participants with Absolute neutrophil count (ANC) should be greater than or equal 1 multiplied by 109 per L in the absence of growth factor support (including granulocyte colony stimulating factors (G-CSF)) or granulocyte transfusions for the previous 4 weeks. Participants with adequate liver function Participants with an ECOG performance status score of 0, 1, or 2. Participants with blasts less than 5 percent in peripheral blood. Assessment of blasts in peripheral blood is mandatory at screening.
Exclusion criteria
Exclusion criteria: Participants who have prior splenectomy at any time or splenic irradiation in the previous 6 months. Participants who have prior hematopoietic cell transplant, or participant anticipated to receive a hematopoietic cell transplant within 24 weeks from the date of randomization Participants who have blasts greater than or equal to 5 percent in bone marrow if results available at screening or history of AP or leukemic transformation. Participants who have evidence of active Hepatitis B Virus (HBV) or Hepatitis C Virus(HCV) infection. Participants who have current or previous positive serology [isolated anti-HBs antibody in IgG will usually signify prior vaccination] results must have negative polymerase chain reaction results. Participants who have active serious infections of bacterial, fungal, parasitic, or viral origin. Participants who have history of a malignancy (other than MF, PV or ET) except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for greater than or equal to 1 year prior to randomization, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for greater than or equal to 3 years. Participants who have history or current diagnosis of ECG or other cardiac abnormalities indicating significant risk of safety Participants who have a gastrointestinal tumor, impaired GI function or GI disease, or significant resection of stomach or other portion of the GI tract, that could significantly alter absorption, including any unresolved nausea, vomiting, or diarrhea. Participants who have severely impaired renal function, had prior treatment with any JAK inhibitor or BET inhibitor, had systemic anti cancer treatment, with the exception of hormonal therapy, less than 14 days before the first dose of study treatment, had hematopoietic growth factor, erythroid maturation agents or androgenic steroids less than 4 weeks before the first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objective in participants with TSS greater than or equal to 25 & with TSS greater than or equal to 15: To determine the efficacy of pelabresib plus ruxolitinib compared with placebo plus ruxolitinib with regard to spleen volume reduction and symptom improvement at Week 24 Timepoint: Spleen response defined as achieving greater than or equal to 35 percent reduction from baseline at Week 24 as measured by (MRI or CT scan) and assessed by central radiology read. Absolute change from baseline in total symptom score (TSS) at Week 24 (MFSAF v4.0). | — |
Secondary
| Measure | Time frame |
|---|---|
| To determine the efficacy of pelabresib plus ruxolitinib compared with placebo plus ruxolitinib with regard to spleen volumeTimepoint: Spleen response defined as achieving greater than or equal to 35 percent reduction in spleen volume (SVR35) from baseline to Week 12, Week 36, Week 48 and thereafter, as measured by MRI (or CT scan) Absolute change from baseline and percentage change from baseline in spleen volume over time Time to first SVR35 response Duration of response defined as the time from first SVR35 response to loss of response for any participant who reaches SVR35 at any time;To determine the efficacy of pelabresib plus ruxolitinib compared with placebo plus ruxolitinib with regard to symptomsTimepoint: Symptom response defined as achieving greater than or equal to 50 percent reduction in total symptom score (TSS50) from baseline to Week 24 as measured by the MFSAF v4.0 Symptom response defined as achieving than or equal to 50 percent reduction in total symptom score (TSS50) from baseline to Week 12, Week 36, Week 48 and thereafter as measured by the MFSAF v4.0 Absolute change from baseline and percentage change from baseline in TSS over time Time to first TSS50 response Duration of TSS50 response defined as the time from first TSS50 response to loss of response for any participant who reaches TSS50 at any time;To determine the efficacy of pelabresib plus ruxolitinib compared with placebo plus ruxolitinib with regard to spleen volume reduction and symptom improvement over time (dual response)Timepoint: Dual response defined as achieving both greater than or equal to 35 percent reduction in spleen volume (SVR35) and greater than or equal to 50 percent reduction in total symptom score (TSS50) from baseline to Week 12, 24, 36, 48 and thereafter with SVR measured by MRI (or CT scan) and assessed by central radiology read and TSS measured by MFSAF v4.0;To determine the effect of pelabresib plus ruxolitinib compared with placebo plus ruxolitinib on | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Japan, Malaysia, Netherlands, New Zealand, Poland, Portugal, Republic of Korea, Singapore, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States of America
Contacts
Public ContactMurugananthan K
Novartis Healthcare Private Limited
Outcome results
None listed