Post Essential Thrombocythaemia Myelofibrosis (PET-MF), Post Polycythemia Myelofibrosis (PPV MF), Primary Myelofibrosis (PMF)
Conditions
Keywords
Ruxolitinib, Ropeginterferon alfa 2b, Myelofibrosis, Ruxolitinib failiure
Brief summary
In this open-label single arm phase 2 study, approximately 20 patients with MF demonstrating suboptimal response to ruxolitinib monotherapy will be enrolled. Patients will continue to receive ruxolitinib at a stable dose and ropeginterferon alfa 2b will be added to the regimen.
Detailed description
Ropeginterferon alfa 2b is administered subcutaneously once every 2 weeks. Ruxolitinib is self-administered orally as part of standard of care. BSubjects will continue combination treatment through the Initial Treatment Period (ITP) (first 6 cycles), which includes a Qualification Assessment. Those deriving clinical benefit in the opinion of the treating physician may continue receiving combination treatment in the Additional Treatment Period (6 cycles). Qualification Assessments will be performed at the end of each Additional Treatment Period, which is iterative, and may repeat for as long as clinical benefit is sustained, at the discretion of the treating physician.
Interventions
Ropeginterferon alfa 2b is administered subcutaneously once every 2 weeks. The dosing will be 250mcg at Week 0, 350mcg at Week 2, 500mcg at Week 4, and 500mcg every 2 weeks thereafter
Sponsors
The University of Hong Kong
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide informed consent * Age ≥18 years * Diagnosis of Overt Myelofibrosis (primary, post-ET, or post-PV) per World Health Organization (WHO) 2022 diagnostic criteria * Intermediate-1, Intermediate-2, or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS) * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * Platelet count ≥75 x 109/L prior to dosing on Cycle 1 Day 1 * Absolute neutrophil count ≥0.5 x 109/L prior to dosing on Cycle 1 Day 1 * Peripheral blast count ≤10% prior to dosing on Cycle 1 Day 1 * Women of childbearing potential and fertile men must agree to use an approved method of contraception from screening until 30 days after the last dose of ropeginterferon and ruxolitinib. * Patients with suboptimal response to ruxolitinib as per one of the below: i. Relapsed: Ruxolitinib treatment for ≥3 months with spleen regrowth, defined as \<10% SVR or \<30% decrease in spleen size from baseline, following an initial response\* ii. Refractory: Ruxolitinib treatment for ≥3 months with \<10% SVR or \<30% decrease in spleen size from baseline. \* Response to ruxolitinib is defined as a ≥35% reduction in spleen volume from baseline, or a ≥50% reduction in spleen size for baseline spleen sizes \>10 cm below left costal margin (LCM); a non-palpable spleen for baseline spleen sizes between 5-10 cm below LCM; or not eligible for spleen response for baseline spleen \<5 cm below LCM.
Exclusion criteria
Subjects will not be eligible for participation if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 24 months | Enumeration and description of adverse events (AEs), including determination of dose limiting toxicities (DLTs), serious adverse events (SAEs), and other AEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Spleen volume change at 24 weeks | 24 weeks | Proportion of patients who experience a spleen length reduction by palpation of ≥30% OR spleen volume reduction (SVR) of ≥35% by MRI or CT by 24 weeks of treatment |
| Symptom response at 24 weeks | 24 weeks | Proportion of patients who describe a ≥50% reduction in symptom burden by the myelofibrosis symptom assessment form (MFSAF) by 24 weeks of treatment. The MFSAF has a scale of 0-70 where a higher score indicates worse outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Rate of molecular responses | 24 months | Changes in allelic burden of JAK2V617F, MPL, CALR or other driver mutations will be assessed. A molecular responses is assessed using the International Working Group of Myeloproliferative Neoplasm Research and Treatment Criteria. |
| Rate of morphologic response | 24 months | Changes in bone marrow morphology (cellularity, erythroid, myeloid, megakaryocyte, reticulin and fibrosis) during treatment. Response is assessed using the International Working Group of Myeloproliferative Neoplasm Research and Treatment Criteria. |
Countries
Hong Kong
Contacts
Primary ContactHainder Gill, MD
Outcome results
None listed