Myelofibrosis Cancer
Conditions
Interventions
Treatment is delivered in 28-day cycles. During an initial pre-treatment stage, patients are established onto a stable dose of fedratinib. The starting dose of 400mg can be reduced in the event of tox
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Age 18 or over at trial entry 2. Confirmed diagnosis of JAK2 V617F positive primary or secondary MF, according to WHO 2016 diagnostic criteria 3. Require treatment, as clinically determined by local investigator 4. Intermediate-2 or high risk according to DIPSS, or intermediate-1 according to DIPSS with palpable splenomegaly >5cm 5. Peripheral blood or bone marrow blasts <10% 6. Adequate blood counts: platelets =75 x10-9/L, neutrophils =1.0 x10-9/L 7. Adequate organ function
Exclusion criteria
Exclusion criteria: 1. Previous treatment with a JAK2 inhibitor or interferon alpha 2. Chemotherapy or biologic therapy within 2 weeks of commencing the trial treatment, or ongoing toxicity relating to prior therapy 3. Blood thiamine concentration below lower limit of normal 4. Active malignancy treated in the last 2 years 5. Pre-existing and uncontrolled thyroid disease, diabetes or autoimmune disease 6. History of severe psychiatric disorder, including severe depression, suicidal ideation and suicide attempt 7. Current severe or uncontrolled cardiovascular disease 8. Previous organ transplantation receiving ongoing immunosuppression 9. Evidence of active HIV, HBV or HCV infection 10. Pregnant and breastfeeding patients and those unwilling to use effective contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tolerability of combination therapy. A patient is classified as not tolerating treatment if they discontinue either fedratinib or ropeginterferon alfa-2b due to drug-related toxicity, due to delays in treatment exceeding 28 consecutive days due to drug-related toxicity, or if a treatment toxicity-related death is reported, within 4 months of starting combination therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Tolerability of combination therapy throughout the treatment course. A patient is classified as not tolerating treatment as per the definition for the primary outcome. 2. Best overall response, defined to be complete or partial response, assessed using IWG criteria (spleen size assessed by palpation) within 12 and 24 months from starting combination therapy. 3. The highest tolerated dose of ropeginterferon alfa-2b, in combination with fedratinib, achieved by each patient. To be tolerated, the dose must have been maintained for at least one complete cycle. 4. Toxicity, defined as the proportion of patients experiencing any grade =3 adverse event, or a serious adverse event of any grade. 5. Overall survival, defined to be time from starting combination therapy to date of death from any cause. 6. Progression-free survival, defined as the time from starting combination therapy to first event or death from any cause. An event here is defined to be any of the following: an increase in bone marrow fibrosis, an increase in spleen size by more than 5cm or transformation to acute myeloid leukaemia. 7. Quality of life, assessed using the MFSAF v2.0 total symptom score at trial entry and at the end of each cycle of treatment 8. JAK2 V617F clone size, measured at trial entry and 3-monthly during treatment. 9. Bone marrow fibrosis, assessed using consensus definitions (Thiele et al. 2005), at trial entry and 6-monthly during treatment. | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Outcome results
None listed