NCT03118492

Combination Chemotherapy, Total Body Irradiation, and Donor Blood Stem Cell Transplant in Treating Patients With Secondary Myelofibrosis

A Pilot Study of Reduced Intensity HLA-Haploidentical Hematopoietic Cell Transplantation With Post-Transplant Cyclophosphamide in Patients With Advanced Myelofibrosis

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This pilot phase I trial studies the side effects of combination chemotherapy, total body irradiation, and donor blood stem cell transplant in treating patients with secondary myelofibrosis. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving combination chemotherapy and total body irradiation before a donor blood stem cell transplant helps to stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the safety and tolerability of reduced-intensity (fludarabine/melphalan) haploidentical hematopoietic cell transplantation (Haplo-HCT) followed by post-transplant cyclophosphamide (PTCy) in patients with advanced myelofibrosis (MF), as assessed by the evaluation of toxicities, including type, frequency, severity, attribution, time course and duration. SECONDARY OBJECTIVES: I. To summarize and evaluate hematologic (neutrophil and platelet) recovery. II. To evaluate and describe cytokine release syndrome (CRS) post haploidentical HCT in the setting of advanced myelofibrosis, as assessed by grade, frequency, severity, duration and reversibility (outcome). III. To estimate graft failure-free survival (GFS) at 100-days post-transplant. IV. To estimate overall survival (OS), progression-free survival (PFS) and cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at 100-days, 1-year, and 2-year post transplant. V. To estimate the cumulative incidence of acute graft-versus-host disease (GvHD), grade II-IV, at 100-days post-transplant (per Keystone Consensus modification of the Glucksberg criteria). VI. To estimate the cumulative incidence of chronic GvHD at 1-year and 2-year post transplant (per National Institutes of Health \[NIH\] Consensus Criteria). VII. To characterize the severity and extent of acute and chronic GvHD. EXPLORATORY OBJECTIVE: I. To conduct correlative studies and describe inflammatory cytokine levels and GVHD biomarker levels in plasma and T cell differentiation/functions in patients enrolled onto the trial. OUTLINE: Patients receive melphalan intravenously (IV) over 30 minutes on day -5, fludarabine IV over 30-60 minutes on days -5 to -2. Patients undergo total body irradiation (TBI) on day -1 and hematopoietic cell transplantation (HCT) on day 0. Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Starting on day 5, patients receive tacrolimus IV then orally (PO) for 6 months followed by a taper, mycophenolate mofetil PO thrice daily (TID) until day 35, and glycosylated recombinant human G-CSF AVI-014 (G-CSF) IV daily until absolute neutrophil count \> 1,500/mm\^3 for 3 consecutive days. Treatment continues in the absence of disease progression or unexpected toxicity. After completion of study treatment, patients are followed for up to 2 years.

Conditions

• Secondary Myelofibrosis

Interventions

Type	Name	Description
PROCEDURE	Allogeneic Hematopoietic Stem Cell Transplantation	Undergo HCT
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine	Given IV
BIOLOGICAL	Glycosylated Recombinant Human G-CSF AVI-014	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Melphalan	Given IV
DRUG	Mycophenolate Mofetil	Given PO
DRUG	Tacrolimus	Given IV or PO
RADIATION	Total-Body Irradiation	Undergo TBI

Timeline

• Start date: 2017-05-24
• Primary completion: 2026-05-26
• Completion: 2026-05-26
• First posted: 2017-04-18
• Last updated: 2025-06-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study