Early Allogeneic Hematopoietic Cell Transplantation in Treating Patients With Relapsed or Refractory High-Grade Myeloid Neoplasms
Condition: Blasts 10 Percent or More of Bone Marrow Nucleated Cells; Chronic Myelomonocytic Leukemia-2; High Grade Malignant Neoplasm; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts-2; Myeloid Neoplasm; Previously Treated Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia
MeSH terms: Leukemia; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      This clinical trial studies how well early stem cell transplantation works in treating
      patients with high-grade myeloid neoplasms that has come back after a period of improvement
      or does not respond to treatment. Drugs used in chemotherapy, such as filgrastim, cladribine,
      cytarabine and mitoxantrone hydrochloride, 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. Giving chemotherapy before a donor peripheral blood cell transplant
      helps 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. The donated stem cells may also replace the patient's immune cells and
      help destroy any remaining cancer cells. Early stem cell transplantation may result in more
      successful treatment for patients with high-grade myeloid neoplasms.
    

Detailed description: 
      OUTLINE:

      RE-INDUCTION CHEMOTHERAPY: Patients receive filgrastim subcutaneously (SC) on days 0-5,
      mitoxantrone hydrochloride intravenously (IV) over 60 minutes on days 1-3, cladribine IV over
      2 hours on days 1-5, and cytarabine IV over 2 hours on days 1-5.

      CONDITIONING REGIMEN: Beginning 14-60 days after re-induction chemotherapy, patients receive
      fludarabine phosphate IV over 30 minutes on days -6 to -2, melphalan IV on days -3 to -2,
      cyclosporine orally (PO) twice daily (BID) starting on day -3. Sirolimus PO BID starting on
      day -3 will be given to patients who have matched unrelated donors or mismatched unrelated
      donors. Patients >55 years or with significant co-morbidities will only receive melphalan IV
      on day -2 and will also receive total body irradiation (TBI) on day -1 or day 0.

      EARLY TRANSPLANT: Patients undergo allogeneic HCT after conditioning regimen on day 0.

      GVHD PROPHYLAXIS: Patients with matched donors will receive mycophenolate mofetil PO three
      times daily (TID) on days 0-30, then twice a day (BID) until day 40; and cyclosporine PO BID
      on days -3 to 96, with a taper until day 150. Patients with matched unrelated donors also
      receive sirolimus PO BID on days -3 to 150, with a taper until day 180. Patients with
      mismatched unrelated donors will receive mycophenolate mofetil PO TID on days 0-30, then BID
      until day 100, with a taper until day 150; cyclosporine PO BID on days -3 to 150, then taper
      until day 180; and sirolimus BID PO days -3 to 180, then a taper until day 365.

      After completion of study treatment, patients are followed up periodically.
    

Intervention name(s): Cladribine; Cyclosporine; Cytarabine; Filgrastim; Fludarabine Phosphate; Allogeneic Hematopoietic Stem Cell Transplantation; Laboratory Biomarker Analysis; Melphalan; Mitoxantrone Hydrochloride; Mycophenolate Mofetil; Questionnaire Administration; Sirolimus; Total-Body Irradiation; Melphalan Hydrochloride
Intervention type(s): Drug; Drug; Drug; Biological; Drug; Procedure; Other; Drug; Drug; Drug; Other; Drug; Radiation; Drug
Intervention description(s): Given IV; Given PO; Given IV; Given SC; Undergo allogeneic hematopoietic stem cell transplantation; Correlative studies; Given IV; Given IV; Given PO; Ancillary studies; Given PO; Undergo TBI; Given IV
Other intervention name(s): 2-CdA; 2CDA; CdA; Cladribina; Leustat; Leustatin; Leustatine; RWJ-26251; 27-400; Ciclosporin; CsA; Cyclosporin; Cyclosporin A; Gengraf; Neoral; OL 27-400; Sandimmun; Sandimmune; SangCya; .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; FILGRASTIM, LICENSE HOLDER UNSPECIFIED; 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; Allogeneic Hematopoietic Stem Cell HSCT; Allogeneic Stem Cell Transplantation; HSC; 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; CL 232315; DHAD; DHAQ; Dihydroxyanthracenedione Dihydrochloride; Mitoxantrone Dihydrochloride; Mitoxantroni Hydrochloridum; Mitozantrone Hydrochloride; Mitroxone; Neotalem; Novantrone; Onkotrone; Pralifan; Cellcept; MMF; AY 22989; RAPA; Rapamune; Rapamycin; SILA 9268A; WY-090217; Total Body Irradiation; Whole-Body Irradiation; 241286; 3-(p-(bis(2-chloroethyl)amino)phenyl)-L-Alanine; Hydrochloride; Alkeran; Alkerana; Evomela
Intervention MeSH terms: Cytarabine; Cyclosporine; Mycophenolic Acid; Sirolimus; Fludarabine; Fludarabine phosphate; Melphalan; Mechlorethamine; Mitoxantrone; Nitrogen Mustard Compounds; Cladribine; 2-chloro-3'-deoxyadenosine; Cyclosporins; Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment