High Dose Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil in Preventing Graft Versus Host Disease in Patients With Hematological Malignancies Undergoing Myeloablative or Reduced Intensity Donor Stem Cell Transplant
Condition: Acute Leukemia; Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Diffuse Large B-Cell Lymphoma; Follicular Lymphoma; Graft Versus Host Disease; Hodgkin Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Secondary Myelodysplastic Syndrome
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; Myelodysplastic Syndromes; Myeloproliferative Disorders; Graft vs Host Disease; Syndrome; Recurrence
Study type: Interventional
Phase: Phase 2

Summary: 
      This pilot phase II trial studies how well high dose cyclophosphamide, tacrolimus, and
      mycophenolate mofetil work in preventing graft versus host disease in patients with
      hematological malignancies undergoing myeloablative or reduced intensity donor stem cell
      transplant. Sometimes the transplanted cells from a donor can make an immune response against
      the body's normal cells (called graft versus host disease). Giving high dose
      cyclophosphamide, tacrolimus, and mycophenolate mofetil after the transplant may stop this
      from happening.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To estimate the graft versus host disease (GVHD)-free relapse/progression-free survival
      (GRFS) at one-year post hematopoietic cell transplantation (HCT) and to evaluate the clinical
      activity of post-transplant high dose cyclophosphamide (PTCy).

      SECONDARY OBJECTIVES:

      I. To summarize toxicities/complications/infections including type, frequency, severity,
      attribution, time course and duration through 100 days post-transplant.

      II. To estimate the cumulative incidence (CI) of acute and chronic GVHD. III. To characterize
      the time course of neutrophil and platelet recovery/engraftment.

      IV. To estimate overall survival (OS), progression-free survival (PFS), CI of
      relapse/progression and non-relapse mortality (NRM) at 100 days, 1 year and 2 years.

      V. To describe quality of life at 100 days, 6 months, 1 and 2 years. VI. To characterize
      immune cell reconstitution and T cell repertoire post high dose cyclophosphamide in
      mismatched donor HCT.

      VII. To characterize quality of life.

      OUTLINE:

      CONDITIONING REGIMEN: Patients are assigned to 1 of 3 conditioning regimens at the discretion
      of the attending physician and principal investigator.

      REGIMEN A (REDUCED INTENSITY CONDITIONING): Patients receive fludarabine phosphate
      intravenously (IV) over 60 minutes on days -7 to -3 and melphalan hydrochloride IV over 20
      minutes on day -2.

      REGIMEN B (MYELOABLATIVE CONDITIONING [MAC]): Patients receive fludarabine phosphate IV over
      1-3 hours and busulfan IV over 3 hour on days -5 to -2.

      REGIMEN C (MAC): Patients receive fludarabine phosphate IV over 60 minutes on days -7 to -5
      and total body irradiation (TBI) twice daily (BID) on days -4 to -1.

      TRANSPLANT: Patients undergo peripheral blood stem cell (PBSC) hematopoietic cell
      transplantation (HCT) on day 0.

      GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4,
      mycophenolate mofetil IV or orally (PO) thrice daily (TID) beginning on day 5 and stopping on
      day 35 if no severe GVHD is present, and tacrolimus IV continuously on days 5-180 with a
      taper beginning on day 90 in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up twice weekly for 100 days,
      twice monthly for 6 months, monthly until no evidence of GVHD, and then yearly for up to 2
      years.
    

Intervention name(s): Busulfan; Cyclophosphamide; Fludarabine Phosphate; Hematopoietic Cell Transplantation; Laboratory Biomarker Analysis; Melphalan Hydrochloride; Mycophenolate Mofetil; Peripheral Blood Stem Cell Transplantation; Quality-of-Life Assessment; Tacrolimus; Total-Body Irradiation
Intervention type(s): Drug; Drug; Drug; Procedure; Other; Drug; Drug; Procedure; Other; Drug; Radiation
Intervention description(s): Given IV; Given IV; Given IV; Undergo PBSC HCT; Correlative studies; Given IV; Given IV or PO; Undergo PBSC HCT; Ancillary studies; Given IV; Undergo TBI
Other intervention name(s): 1, 4-Bis[methanesulfonoxy]butane; BUS; Bussulfam; Busulfanum; Busulfex; Busulphan; CB 2041; CB-2041; Glyzophrol; GT 41; GT-41; Joacamine; Methanesulfonic Acid Tetramethylene Ester; Methanesulfonic acid, tetramethylene ester; Mielucin; Misulban; Misulfan; Mitosan; Myeleukon; Myeloleukon; Myelosan; Mylecytan; Myleran; Sulfabutin; Tetramethylene Bis(methanesulfonate); Tetramethylene bis[methanesulfonate]; WR-19508; (-)-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; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; 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 transplantation; Alkeran; Alkerana; Evomela; Cellcept; MMF; PBPC transplantation; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplant; Peripheral Stem Cell Transplantation; Quality of Life Assessment; FK 506; Fujimycin; Hecoria; Prograf; Protopic; TOTAL BODY IRRADIATION; Whole-Body Irradiation
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Melphalan; Busulfan; Fludarabine; Fludarabine phosphate; Tacrolimus
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care