Combination Chemotherapy and Donor Stem Cell Transplant in Treating Patients With Aplastic Anemia or Hematologic Cancer
Condition: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Nonmalignant Neoplasm; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Lymphoma; Neoplasms; Leukemia; Preleukemia; Anemia; Myelodysplastic Syndromes; Anemia, Aplastic; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      RATIONALE: Giving chemotherapy drugs and total-body irradiation before a donor stem cell
      helps stop the growth of cancer or abnormal cells. It may also stop the patient's immune
      system from rejecting the donor's stem 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. It is not yet known which combination chemotherapy
      regimen is most effective when given before a donor stem cell transplant in treating aplastic
      anemia or hematologic cancer.

      PURPOSE: This phase II/III trial is studying different combination chemotherapy regimens to
      compare how well they work when given before donor stem cell transplant in treating patients
      with aplastic anemia or hematologic cancer.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the morbidity, mortality, and overall outcome of patients with severe aplastic
           anemia or hematologic malignancy treated with standard vs novel conditioning regimens
           followed by allogeneic stem cell transplantation.

        -  Examine the influence of donor histocompatibility on outcome by comparing
           matched/related, mismatched/related (with or without T-cell depletion), and
           matched/unrelated transplants with stratification for type of preparative regimen.

        -  Ensure that patients with uncommon diagnoses will be treated in a uniform fashion with
           the best therapy available.

      OUTLINE: Patients are stratified according to risk of relapse (standard-risk: acute leukemia
      in first complete remission, chronic myelogenous leukemia in first chronic phase, lymphoma in
      sensitive first relapse or second remission, primary or untreated myelodysplastic syndromes,
      or untreated severe aplastic anemia vs high-risk: all others).

      Patients are assigned to one of the following conditioning regimens based on diagnosis, risk
      of relapse, and donor relatedness:

        -  Regimen 1: Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 and
           cyclophosphamide IV over 2 hours on days -3 and -2.

        -  Regimen 2: Patients receive cyclophosphamide IV over 2 hours on days -5 to -2 and
           anti-thymocyte globulin IV over 4-8 hours on days -5 to -3.

        -  Regimen 3: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and
           total-body irradiation (TBI) twice daily on days -3 to -1.

        -  Regimen 4: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and
           melphalan IV over 1 hour on days -3 and -2.

        -  Regimen 5: Patients receive etoposide IV over 26 hours beginning on day -5,
           cyclophosphamide IV over 2 hours on day -4, and TBI twice daily on days -3 to -1.

        -  Regimen 6: Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24
           hours, and thiotepa IV over 24 hours on days -7 to -4.

        -  Regimen 7: Patients receive fludarabine IV over 30 minutes on days -5 to -1 and
           anti-thymocyte globulin IV over 4-8 hours on days -5 to -2.

        -  Regimen 8: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4, TBI
           twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4-8 hours on days -3
           to -1.

        -  Regimen 9: Patients receive busulfan IV over 2 hours every 6 hours and anti-thymocyte
           globulin IV over 4-8 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days
           -3 and -2.

      All patients then receive donor stem cell infusions on day 0. Some patients may undergo
      involved-field radiotherapy 4-8 weeks after transplant.

      Patients will be taken off study after a minimum of 4 years of follow up.

      PROJECTED ACCRUAL: At least 405 patients will be accrued for this study within 5 years.
    

Intervention name(s): anti-thymocyte globulin; busulfan; carboplatin; cyclophosphamide; etoposide; fludarabine phosphate; melphalan; thiotepa; total-body irradiation
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Radiation
Intervention description(s): Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Given IV; Given twice daily for 3 days
Intervention MeSH terms: Cyclophosphamide; Melphalan; Busulfan; Thiotepa; Carboplatin; Fludarabine; Fludarabine phosphate; Etoposide; Antilymphocyte Serum
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent childhood acute lymphoblastic leukemia; recurrent cutaneous T-cell non-Hodgkin lymphoma; Burkitt lymphoma; Waldenstrom macroglobulinemia; recurrent childhood lymphoblastic lymphoma; recurrent childhood acute myeloid leukemia; recurrent adult acute myeloid leukemia; recurrent adult acute lymphoblastic leukemia; relapsing chronic myelogenous leukemia; refractory chronic lymphocytic leukemia; chronic phase chronic myelogenous leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; adult acute myeloid leukemia in remission; adult acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; childhood acute lymphoblastic leukemia in remission; polycythemia vera; essential thrombocythemia; refractory anemia; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; chronic myelomonocytic leukemia; T-cell large granular lymphocyte leukemia; acute undifferentiated leukemia; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent adult Burkitt lymphoma; recurrent adult T-cell leukemia/lymphoma; secondary acute myeloid leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; prolymphocytic leukemia; intraocular lymphoma; recurrent childhood small noncleaved cell lymphoma; recurrent childhood large cell lymphoma; recurrent mantle cell lymphoma; angioimmunoblastic T-cell lymphoma; anaplastic large cell lymphoma; recurrent mycosis fungoides/Sezary syndrome; primary myelofibrosis; childhood chronic myelogenous leukemia; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12); childhood myelodysplastic syndromes; aplastic anemia; unspecified adult solid tumor, protocol specific; unspecified childhood solid tumor, protocol specific