Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies
Condition: Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Myeloid Leukemia in Remission; Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia
MeSH terms: Burkitt Lymphoma; Mycoses; Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Leukemia, Myeloid, Acute; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Preleukemia; Neoplasm Metastasis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, B-Cell; Hodgkin Disease; Lymphoma, Mantle-Cell; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, B-Cell, Marginal Zone; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Mycosis Fungoides; Sezary Syndrome; Leukemia, T-Cell; Lymphoma, T-Cell, Cutaneous; Waldenstrom Macroglobulinemia; Leukemia-Lymphoma, Adult T-Cell; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Lymphoma, Large-Cell, Anaplastic; Leukemia, Myeloid, Chronic-Phase; Blast Crisis; Lymphomatoid Granulomatosis; Leukemia, Myeloid, Accelerated Phase; Lymphoma, Extranodal NK-T-Cell; Leukemia, Megakaryoblastic, Acute; Leukemia, Erythroblastic, Acute; Intraocular Lymphoma; Myelodysplastic Syndromes; Lymphoproliferative Disorders; Immunoblastic Lymphadenopathy; Graft vs Host Disease; Syndrome; Recurrence; Philadelphia Chromosome
Intervention: cyclophosphamide; cyclosporine; peripheral blood stem cell transplantation; total-body irradiation; fludarabine phosphate; busulfan; allogeneic hematopoietic stem cell transplantation
Intervention description: Given IV; Given IV; Undergo allogeneic PBSCT; Undergo TBI; Given IV; Given IV; Undergo allogeneic PBSCT
Intervention MeSH terms: Cyclosporine; Cyclophosphamide; Busulfan; Fludarabine; Fludarabine phosphate; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well cyclophosphamide works in preventing chronic
      graft-versus-host disease after allogeneic peripheral blood stem cell transplant in patients
      with hematological malignancies. Giving chemotherapy and total-body irradiation before
      transplantation helps stop the growth of cancer cells and prevents the patient's immune
      system from rejecting the donor's stem cells. Healthy stem cells from a donor that are
      infused into the patient help the patient's bone marrow make blood cells; red blood cells,
      white blood cells, and platelets. Sometimes, however, the transplanted donor cells can cause
      an immune response against the body's normal cells, which is called graft-versus-host disease
      (GVHD). Giving cyclophosphamide after transplant may prevent this from happening or may make
      chronic GVHD less severe.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Acute lymphocytic leukemia (ALL) in morphologic first complete remission (CR1) with
             high risk features defined as, but not limited to: evidence of adverse cytogenetics
             such as t(9;22), t(1;19), t(4;11), or mixed-lineage leukemia (MLL) rearrangements;
             presence of minimal residual disease; progenitor B-cell immunophenotype; high white
             blood cells (WBC) at diagnosis (> 30,000/ul in B-ALL; > 100,000/ul in T-ALL); or
             delayed attainment of CR (> 4 weeks) after induction therapy; additional clinical
             characteristics deemed to confer a high relapse risk may be discussed with and
             approved by the Principal Investigator (PI)

          -  Acute myeloid leukemia (AML) in CR1 EXCEPT patients with low-risk features defined as:

               -  Inv 16 or t(8;21) in the absence of c-kit mutations

               -  Normal karyotype who are FLT3-ITD-negative and NPM1-positive in the absence of
                  c-kit mutations

               -  Patients with respective "low-risk" features are eligible, however, if (i) more
                  than 1 cycle of induction therapy was required to achieve CR1 (ii) the patient
                  had a preceding myelodysplastic syndrome (MDS) other than myelofibrosis, or (iii)
                  secondary AML

          -  Acute leukemia in 2nd or greater CR (CR >= 2)

          -  Refractory or relapsed AML with =< 10% bone marrow blasts and no circulating blasts or
             proven extramedullary disease

          -  AML transformed from myelodysplastic syndrome (MDS) with < 10% bone marrow blasts

          -  MDS with following high risk features:

               -  High risk cytogenetics (including, but not limited to: 7q--, inv[3], t[3q],
                  del[3q] or complex karyotype)

               -  International Prognostic Scoring System (IPSS) intermediate (INT)-2 or greater

               -  Treatment-related MDS

               -  Any phase of MDS if patient is < 21 years of age

          -  Chronic myelogenous leukemia (CML) beyond 1st chronic phase or resistant or intolerant
             to tyrosine kinase inhibitors (adults) or any phase (pediatric < 21 years)

          -  Chronic myelomonocytic leukemia

          -  Philadelphia-negative myeloproliferative disorder

          -  Lymphoma: relapsed chemotherapy-sensitive (complete or partial response) Hodgkin or
             non-Hodgkin lymphoma

          -  Multiple myeloma-stage III

          -  The patient or legal representative must be able to understand and give written
             informed consent

          -  DONORS: The donor must be a genotypically HLA-identical sibling, a phenotypically
             HLA-matched first-degree relative, or an unrelated donor who is molecularly matched
             with the patient at HLA-A, B, C, DRB1

          -  DONORS: Donors must meet the selection criteria for administration of G-CSF
             (filgrastim) and apheresis defined by the Foundation for the Accreditation of Cell
             Therapy (FACT) and will be screened per the American Association of Blood Banks (AABB)

          -  DONORS: Donors must be capable of giving informed consent

        Exclusion Criteria:

          -  Prior autologous or allogeneic stem cell transplant

          -  Performance status > 2 (Eastern Cooperative Oncology Group [ECOG]) or < 50 (Lansky;
             for patients < 16 years old)

          -  Uncontrolled infection; the protocol principal investigator (PI) will be final arbiter
             if there is uncertainty regarding whether a previous infection is under adequate
             control to allow enrollment in the study

          -  Positive serology for human immunodeficiency virus (HIV)-1, 2 or human T cell
             lymphotropic virus (HTLV)-1, 2

          -  Left ventricular ejection fraction < 45% or shortening fraction < 25%; no uncontrolled
             arrhythmias or symptomatic cardiac disease

          -  Symptomatic pulmonary disease; forced expiratory volume in one second (FEV1), forced
             vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO) =< 50%
             of predicted (corrected for hemoglobin); if pulmonary function tests cannot be
             performed, an oxygen saturation < 92% on room air

          -  Calculated (Cockcroft-Gault or appropriate calculation for pediatric patients) serum
             creatinine clearance =< 60 mL/min; if the calculated CrCl is 50-60 mL/min, but a
             measured CrCl by 24 hour urine collection is > 60 mL/min, this measurement is
             acceptable

          -  Total serum bilirubin more than twice upper normal limit

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3-fold
             higher than laboratory upper normal limits

          -  Female patient must have negative serum pregnancy test (all women of child
             bearing-potential must have test performed)

          -  DONORS: Potential donors who for psychological, physiological, or medical reasons
             cannot tolerate administration of G-CSF or apheresis

          -  DONORS: Donors who are allergic to filgrastim or Escherichia (E.) coli-derived
             proteins

          -  DONORS: Donor-related risks to recipients

          -  DONORS: Positive anti-donor lymphocytotoxic crossmatch

          -  DONORS: Donors who are positive for HIV