NCT04370301

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Detailed description

OUTLINE: Cohort 1 is now closed and all patients will be enrolled on Cohort 2. COHORT I: JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of hematopoietic cell transplantation (HCT) conditioning through day -4 before transplantation. CONDITIONING: Patients receive melphalan intravenously (IV) over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo total-body irradiation (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 orally (PO) for about 6 months, mycophenolate mofetil PO twice daily (BID) or three times daily (TID) beginning day 5 for 6 weeks, and granulocyte colony-stimulating factor (G-CSF) subcutaneously (SC) beginning day 7 until neutrophil recovery is \> 1,500/mm\^3. COHORT II: JAK 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 magnetic resonance imaging (MRI), computed tomography (CT), bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) on the trial. After completion of study treatment, patients are followed up between day 80-100, at 1 year, and then up to 5 years.

Conditions

• Primary Myelofibrosis
• Secondary Myelofibrosis

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given IV
DRUG	JAK Inhibitor	Given PO
DRUG	Fludarabine	Given IV
BIOLOGICAL	Recombinant Granulocyte Colony-Stimulating Factor	Given SC
DRUG	Melphalan	Given IV
DRUG	Mycophenolate Mofetil	Given PO
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Given IV
DRUG	Tacrolimus	Given IV and PO
RADIATION	Total-Body Irradiation	Undergo TBI
PROCEDURE	Computed Tomography	Undergo CT
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy and aspiration
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow biopsy and aspiration
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Echocardiography Test	Undergo ECHO
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA

Timeline

• Start date: 2021-02-09
• Primary completion: 2027-04-30
• Completion: 2029-08-31
• First posted: 2020-04-30
• Last updated: 2026-01-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study