Reduced Intensity Haploidentical Transplantation for the Treatment of Primary or Secondary Myelofibrosis
Pilot Study of JAK Inhibitor Therapy Followed by Reduced Intensity Haploidentical Transplantation for Patients With Myelofibrosis
3 other identifiers
interventional
20
1 country
1
Brief Summary
This initial cohort of this phase II trial studied the outcomes of using a JAK inhibitor prior to reduced intensity haploidentical (Haplo) transplantation for the treatment of primary or secondary myelofibrosis (MF). The primary risk of using Haplo HCT in patients with MF is graft failure. In the first cohort, all patients engrafted. There were no instances of graft failure. However, a large number of patients did have graft versus host disease as a complication of their transplant. JAK inhibitors have since been approved for the indication of graft versus host disease treatment. And we are also using them for graft versus host disease prevention in a study of MF patients with sibling and unrelated donors. Therefore, we are opening a new cohort of the current study using the JAK inhibitor prior to, during and after Haplo transplant. Our goal is to decrease graft versus host disease in patients receiving a Haplo MF transplant without increasing the risk of graft failure.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Feb 2021
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 28, 2020
CompletedFirst Posted
Study publicly available on registry
April 30, 2020
CompletedStudy Start
First participant enrolled
February 9, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2029
January 12, 2026
January 1, 2026
6.2 years
April 28, 2020
January 8, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Probability of primary and secondary graft failure
Primary graft failure is defined as failure to achieve an absolute neutrophil count of \> 500/ul by 42 days after bone marrow or peripheral blood stem cell transplantation. Secondary graft failure is defined as cytopenias after initial engraftment, with (a) donor chimerism of \< 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism is \> 5%. Exclusion criteria for diagnosis of graft failure are (a) disease relapse, (b) graft-versus-host disease, and (c) other causes of cytopenias such as, viral infection and drug toxicity.
Up to 5 years
Secondary Outcomes (9)
Incidence of severe (grade 3 or 4) cytokine release syndrome
Up to 5 years
Non-relapse mortality (NRM)
Day 100
NRM
1 year
Overall survival
1 year
Overall survival
3 years
- +4 more secondary outcomes
Study Arms (2)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
EXPERIMENTALJAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0. TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0. GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is \> 1,500/mm\^3. All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
EXPERIMENTALJAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant. CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0. TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0. GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is \> 1,500/mm\^3. All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
Interventions
Given SC
Given IV
Undergo TBI
Undergo CT
Undergo MRI
Undergo bone marrow biopsy and aspiration
Undergo bone marrow biopsy and aspiration
Undergo ECHO
Undergo MUGA
Given IV
Given PO
Given IV
Given IV
Given PO
Given IV and PO
Undergo blood sample collection
Eligibility Criteria
You may qualify if:
- Age between 18 and 70 years
- Diagnosis of primary myelofibrosis (PMF) as defined by the 2016 World Health Organization classification system or diagnosis of secondary 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 the Dynamic International Prognostic Scoring System (DIPSS)-plus scoring system (DIPSS may be used if all data from DIPSS are not available)
- Ability to understand and the willingness to sign a written informed consent document (or legally authorized representative)
- Patient must be a potential hematopoietic stem cell transplant candidate
- Meeting criteria for 1st phase as above, at time of initiation of JAK inhibitor, including ability to understand and willingness to sign a written informed consent (or legally authorized representative). Patients arriving to our institution for transplant and not enrolled in Part 1 may still be enrolled in Part 2 if Part 1 criteria met. These patients will have Part 1 endpoints transcribed from medical records
- Received JAK inhibitor for at least 8 weeks immediately prior to conditioning and be willing to continue until 9-12 months post-transplant as tolerated
- Karnofsky performance status score \>= 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 \> 3 mg/dL, and symptomatic biliary disease will be excluded
- Diffusion capacity of the lung for carbon monoxide (DLCO) corrected \> 60% normal; may not be on supplemental oxygen
- Left ventricular ejection fraction \> 40% OR shortening fraction \> 26%
- Comorbidity Index \< 5 at the time of pre-transplant evaluation
- +4 more criteria
You may not qualify if:
- Contraindication to receiving a JAK inhibitor 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)
- Uncontrolled viral or bacterial infection at the time of study enrollment
- Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
- Known HIV positivity
- Pregnant or breastfeeding
- Availability of an human leukocyte antigen (HLA)-identical or 1-allele-mismatched related donor or an HLA 10 of 10 matched unrelated donor
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rachel B. Salit
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 28, 2020
First Posted
April 30, 2020
Study Start
February 9, 2021
Primary Completion (Estimated)
April 30, 2027
Study Completion (Estimated)
August 31, 2029
Last Updated
January 12, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share