Combination Chemotherapy, Total Body Irradiation, and Donor Blood Stem Cell Transplant in Treating Patients With Primary or Secondary Myelofibrosis
Condition: Primary Myelofibrosis; Secondary Myelofibrosis
MeSH terms: Neoplasm Metastasis; Primary Myelofibrosis
Study type: Interventional
Phase: Early Phase 1

Summary: 
      This early phase I trial studies the side effects of combination chemotherapy, total body
      irradiation, and donor blood stem cell transplant in treating patients with primary or
      secondary myelofibrosis. Drugs used in chemotherapy, such as melphalan, fludarabine
      phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil, and filgrastim 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 (FM) 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 estimate
      graft failure-free survival (GFS) at 100-days post-transplant. III. 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.

      IV. 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).

      V. To estimate the cumulative incidence of chronic GvHD at 1-year and 2-year post transplant
      (per National Institute of Health [NIH] Consensus Criteria).

      VI. To characterize the severity and extent of acute and chronic GvHD.

      OUTLINE:

      Patients receive melphalan intravenously (IV) over 30 minutes on days -5, fludarabine
      phosphate IV over 1 hour on days -5 to -2. Patients undergo total body irradiation (TBI) on
      day -1 and hematopoietic stem cell transplant (HCT) on day 0. Patients then receive
      cyclophosphamide IV over 1-2 hours on days 3 and 4. Beginning on day 5, patients receive
      tacrolimus IV continuously for approximately 2 weeks, then orally (PO) for 6 months followed
      by a taper, mycophenolate mofetil PO thrice daily (TID) until day 100, and filgrastim
      subcutaneously (SC) daily from day 7 until continued until absolute neutrophil count (ANC) >
      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 up at 1, 3, 6, 9, 12 and 24
      months.
    

Intervention name(s): Cyclophosphamide; Filgrastim; Fludarabine Phosphate; Hematopoietic Cell Transplantation; Melphalan; Mycophenolate Mofetil; Tacrolimus; Total-Body Irradiation
Intervention type(s): Drug; Biological; Drug; Procedure; Drug; Drug; Drug; Radiation
Intervention description(s): Given IV; Given SC; Given IV; Undergo HCT; Given IV; Given PO; IV or PO; Undergo TBI
Other intervention name(s): (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; G-CSF; Neupogen; r-metHuG-CSF; Recombinant Methionyl Human Granulocyte Colony Stimulating Factor; rG-CSF; Tevagrastim; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; SH T 586; HCT; Hematopoietic Stem Cell Transplantation; HSCT; Stem Cell Transplant; stem cell transplantation; Alanine Nitrogen Mustard; CB-3025; L-PAM; L-Phenylalanine Mustard; L-sarcolysin; L-Sarcolysin Phenylalanine mustard; L-Sarcolysine; Melphalanum; Phenylalanine Mustard; Phenylalanine nitrogen mustard; Sarcoclorin; Sarkolysin; WR-19813; Cellcept; MMF; FK 506; Fujimycin; Hecoria; Prograf; Protopic; TBI; TOTAL BODY IRRADIATION; Whole Body Irradiation; Whole-Body Irradiation
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Melphalan; Mechlorethamine; Nitrogen Mustard Compounds; Fludarabine; Fludarabine phosphate; Tacrolimus; Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment