RECRUITING

Peritransplant Ruxolitinib for Patients With Primary and Secondary Myelofibrosis

Conditions

Primary Myelofibrosis Secondary Myelofibrosis

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase II trial studies how well administering ruxolitinib before, during, and after allogeneic hematopoietic stem cell transplantation works in preventing graft versus host disease and improving transplant outcomes in patients with primary and secondary myelofibrosis. Donor hematopoietic stem cell transplantation (HSCT) is currently the only treatment with proven curative potential for myelofibrosis, however, myelofibrosis patients have a high risk for developing graft versus host disease post-transplant. Graft versus host disease is a condition where the transplanted cells from a donor can attack the body's normal cells. Ruxolitinib, a janus-associated kinase (JAK) inhibitor, is known to decrease inflammatory signals, which may reduce spleen size and decrease symptoms such as night sweats and weight loss. Administering ruxolitinib before, during, and after transplant may decrease the incidence and severity of graft versus host disease, increase survival, and improve quality of life in patients with primary and secondary myelofibrosis.

Official Title

Peritransplant Ruxolitinib for Patients With Primary and Secondary Myelofibrosis

Quick Facts

Study Start:2020-12-18

Study Completion:2029-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04384692

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

Rachel B. Salit

CONTACT

206.667.1317

rsalit@fredhutch.org

Principal Investigator

Rachel B. Salit

PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Study Locations (Sites)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Fred Hutchinson Cancer Center

Rachel B. Salit, PRINCIPAL_INVESTIGATOR, Fred Hutch/University of Washington Cancer Consortium

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-12-18

Study Completion Date2029-12-31

Study Record Updates

Study Start Date2020-12-18

Study Completion Date2029-12-31

Terms related to this study

Additional Relevant MeSH Terms

Primary Myelofibrosis
Secondary Myelofibrosis