Total-Body Irradiation and Cyclophosphamide in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer and Other Diseases
Condition: Leukemia; Lymphoma; Myelodysplastic Syndromes
MeSH terms: Lymphoma; Leukemia; Preleukemia; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Giving total-body irradiation and chemotherapy, such as cyclophosphamide, before a
      donor stem cell transplant helps stop the patient's immune system from rejecting the donor's
      stem cells and helps stop the growth of cancer or abnormal 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. Sometimes the transplanted cells
      from a donor can make an immune response against the body's normal cells. Giving
      immunosuppressive therapy before or after transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well giving total-body irradiation together with
      cyclophosphamide works in treating patients who are undergoing donor stem cell transplant for
      hematologic cancer and other diseases.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Evaluate the potential efficacy of targeting cyclophosphamide to a metabolic endpoint
           when given together with total-body irradiation, in terms of day 200 nonrelapse
           mortality, in patients with hematologic cancer and other diseases who are undergoing
           allogeneic hematopoietic stem cell transplantation.

      Secondary

        -  Determine the overall survival of patients treated with this regimen.

        -  Determine the rate of relapse in patients treated with this regimen.

        -  Determine the occurrence of sinusoidal obstruction syndrome in patients treated with
           this regimen.

        -  Determine the occurrence of acute renal failure in these patients.

        -  Determine the occurrence of respiratory failure in these patients.

      OUTLINE:

        -  Conditioning regimen: Patients undergo total-body irradiation twice daily on days -6 to
           -4. Patients also receive cyclophosphamide IV over 1 hour on day -3 and then IV at a
           metabolism-based dose* on day -2.

      NOTE: *Patients undergo frequent blood sampling after completion of the first
      cyclophosphamide infusion for pharmacokinetic studies in order to determine the dose for the
      second cyclophosphamide infusion.

        -  Allogeneic stem cell transplantation: Patients undergo allogeneic bone marrow or
           peripheral blood stem cell transplantation on day 0.

        -  Graft-versus-host disease (GVHD) prophylaxis: Patients receive GVHD prophylaxis as per
           the attending physician, including one of the following regimens: cyclosporine and
           methotrexate; tacrolimus and methotrexate; tacrolimus and mycophenolate mofetil; or
           sirolimus, tacrolimus, and methotrexate (as per the GVHD prophylaxis regimen chosen for
           each patient).

      After completion of study treatment, patients are followed periodically for at least 200
      days.

      PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
    

Intervention name(s): cyclophosphamide; cyclosporine; methotrexate; mycophenolate mofetil; sirolimus; tacrolimus; pharmacological study; allogeneic bone marrow transplantation; allogeneic hematopoietic stem cell transplantation; peripheral blood stem cell transplantation; total-body irradiation
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Other; Procedure; Procedure; Procedure; Radiation
Intervention MeSH terms: Cyclosporine; Sirolimus; Mycophenolic Acid; Cyclophosphamide; Methotrexate; Tacrolimus; Cyclosporins
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; blastic phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; de novo myelodysplastic syndromes; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; noncontiguous stage II adult Burkitt lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; noncontiguous stage II adult diffuse small cleaved cell lymphoma; noncontiguous stage II adult immunoblastic large cell lymphoma; noncontiguous stage II adult lymphoblastic lymphoma; noncontiguous stage II grade 1 follicular lymphoma; noncontiguous stage II grade 2 follicular lymphoma; noncontiguous stage II grade 3 follicular lymphoma; noncontiguous stage II mantle cell lymphoma; noncontiguous stage II marginal zone lymphoma; noncontiguous stage II small lymphocytic lymphoma; previously treated myelodysplastic syndromes; recurrent adult acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; recurrent adult Burkitt lymphoma; recurrent adult Hodgkin lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic 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; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; secondary myelodysplastic syndromes; splenic marginal zone lymphoma; stage III adult Burkitt lymphoma; stage III adult Hodgkin lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage III marginal zone lymphoma; stage III small lymphocytic lymphoma; stage IV adult Burkitt lymphoma; stage IV adult Hodgkin lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage IV small lymphocytic lymphoma