Using ruxolitinib to improve outcomes for patients with myelofibrosis undergoing stem cell transplantation
Peritransplant Ruxolitinib for Patients With Primary and Secondary Myelofibrosis
This study is testing if giving ruxolitinib to patients with myelofibrosis before, during, and after a stem cell transplant can help them have better outcomes and reduce complications like graft versus host disease.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Fred Hutchinson Cancer Center Academic / other |
| Drugs / interventions | ruxolitinib, methotrexate, cyclophosphamide, fludarabine |
| Locations | 1 site (Seattle, Washington) |
| Trial ID | NCT04384692 on ClinicalTrials.gov |
What this trial studies
This phase II trial investigates the effectiveness of ruxolitinib, a JAK inhibitor, in patients with primary and secondary myelofibrosis who are undergoing allogeneic hematopoietic stem cell transplantation (HSCT). The study involves administering ruxolitinib before, during, and after the transplant to prevent graft versus host disease (GVHD) and enhance transplant outcomes. Patients will receive ruxolitinib starting 8 weeks prior to HSCT, followed by conditioning regimens that may include various chemotherapy agents. The goal is to reduce the incidence and severity of GVHD, improve survival rates, and enhance the quality of life for these patients.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older diagnosed with primary or secondary myelofibrosis who are eligible for hematopoietic stem cell transplantation.
Not a fit: Patients with low-risk myelofibrosis or those not eligible for stem cell transplantation may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve transplant outcomes and reduce complications for patients with myelofibrosis.
How similar studies have performed: Other studies have shown promising results with JAK inhibitors in similar contexts, suggesting potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age \>= 18 years * JAK INHIBITOR ADMINISTRATION INCLUSION: (PART I) * Disease criteria: * Diagnosis of primary myelofibrosis (PMF) as defined by the 2016 World Health Organization classification system or diagnosis of secondary myelofibrosis (MF) as defined by the International Working Group (IWG) for Myeloproliferative Neoplasms Research and Treatment criteria * Patients meeting the criteria for intermediate-1, intermediate-2 or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS) or DIPSS plus * Ability to understand and the willingness to sign a written informed consent document * Patient must be a potential hematopoietic stem cell transplant candidate as assessed by the consenting physician * Patient must be willing to start ruxolitinib within a 6-month time period * ALLOGENEIC STEM CELL TRANSPLANT INCLUSION: (PART II) * Meeting criteria for part 1, as above, at time of initiation of ruxolitinib, including the ability to understand and willingness to sign a written informed consent. Patients arriving to our institution for transplant and not enrolled in part 1 may still be enrolled in part 2 if part 1 criteria are met. These patients will have part 1 endpoints transcribed from medical records * Received ruxolitinib for at least 8 weeks immediately prior to conditioning and be willing to continue until 9-12 months post-transplant as tolerated * Performance status score: Karnofsky \>= 70 * Calculated creatinine clearance using the Cockcroft-Gault formula or 24 hour (hr) urine creatinine clearance must be \> 60 ml/min * Total serum bilirubin must be \< 3 mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis * Transaminases must be \< 3 x the upper limit of normal * Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension. Patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3mg/dL, and symptomatic biliary disease will be excluded * Diffusion capacity of lung for carbon monoxide (DLCO) corrected \> 60% normal. May be not be on supplemental oxygen * Left ventricular ejection fraction \> 40% OR shortening fraction \> 26% * Comorbidity index \< 5 at the time of pre-transplant evaluation Exclusion Criteria: * JAK INHIBITOR ADMINISTRATION EXCLUSION: (PART I) * Contraindication to receiving ruxolitinib including: * Patients who have known hypersensitivity to JAK inhibitors * Clinical or laboratory evidence of significant renal or hepatic impairment including cirrhosis * Active uncontrolled infection * Known human immunodeficiency virus (HIV) positivity * Women who are pregnant or trying to conceive * Caution should be used in patients with platelets \< 100 though adjustments in dose can be made to accommodate anyone with platelets \> 50 * History of prior allogeneic transplant * Leukemic transformation (\> 20% blasts) * ALLOGENEIC STEM CELL TRANSPLANT EXCLUSION: (PART II) * Uncontrolled viral or bacterial infection at the time of transplant data review and consent conference * Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval * History of HIV infection * Pregnant or breastfeeding * Patients without a human leukocyte antigen (HLA)-identical sibling donor, 10 of 10 HLA-matched or 9 of 10 allele mismatched unrelated donor, or umbilical cord blood units that meet transplant criteria
Where this trial is running
Seattle, Washington
- Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)
Study contacts
- Principal investigator: Rachel B. Salit — Fred Hutch/University of Washington Cancer Consortium
- Study coordinator: Rachel B. Salit
- Email: rsalit@fredhutch.org
- Phone: 206.667.1317
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.