Bone Marrow Transplant in Treating Patients With Hematologic Cancers
Condition: Chronic Myeloproliferative Disorders; Leukemia; Multiple Myeloma and Malignant Plasma Cell Neoplasms; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms
MeSH terms: Leukemia; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Giving chemotherapy drugs and total-body irradiation before a donor bone marrow
      transplant helps stop the growth of cancer cells. It also helps 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.

      PURPOSE: This phase II trial is studying how well donor bone marrow transplant works in
      treating patients with hematologic cancers.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the progression free survival (PFS) and overall survival (OS) of patients with
           low risk myeloid disorders or older allogeneic recipients who are treated with high dose
           busulfan and cyclophosphamide and allogeneic bone marrow transplantation (BMT).

        -  Determine the PFS and OS in patients with lymphoid and high risk myeloid disorders who
           are treated with etoposide, total body irradiation, and allogeneic BMT.

        -  Evaluate the toxicities of these 2 regimens when combined with cyclosporine and
           methotrexate as graft versus host disease prophylaxis in these patients.

        -  Evaluate the PFS and OS of allogeneic BMT in patients with multiple myeloma and chronic
           lymphocytic leukemia.

      OUTLINE:

        -  Regimen A: Patients with chronic myelogenous leukemia (CP1, AP/CP2) and other
           myeloproliferative disorders, myelodysplastic disorders, acute myelogenous leukemia
           (CR1), or multiple myeloma (not eligible to receive total body irradiation due to prior
           radiation) are treated with high dose busulfan and cyclophosphamide followed by
           allogeneic bone marrow transplantation (BMT). Patients receive oral busulfan every 6
           hours on days -7 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Allogeneic
           bone marrow is infused on day 0.

        -  Regimen B: Patients with acute myelogenous leukemia (at least CR2, relapsed), acute
           lymphoid leukemia (ALL), any acute leukemia with CNS involvement, multiple myeloma, or
           chronic lymphocytic leukemia are treated with total body irradiation and etoposide
           followed by allogeneic BMT. Patients receive total body irradiation (TBI) on days -7 to
           -4 for a total of 11 fractions and etoposide IV over 4 hours on day -3. Male patients
           with ALL receive a testicular boost in 2 fractions on 2 successive days during TBI.
           Allogeneic bone marrow is infused on day 0.

      Patients in both regimens receive cyclosporine and methotrexate as graft versus host disease
      prophylaxis.

      Patients are followed weekly for 3 months and then monthly for 1 year.

      PROJECTED ACCRUAL: At least 50 patients with low risk myeloid disease, 50 patients with
      lymphoid malignancies, and 60 patients with high risk myeloid disease will be accrued for
      this study.
    

Intervention name(s): busulfan; Cyclophosphamide; VP-16; Fractionated Total Body Irradiation (FTBI)
Intervention type(s): Drug; Drug; Drug; Radiation
Intervention description(s): administered on Day -7 through Day -4. The total dose is 12.8 mg/kg; administered at a dose of 60 mg/kg on each of two successive days (Days -3 and -2); administered as a single infusion on Day -3. The dose is 60 mg/kg and is calculated on actual body weight unless the patient's weight is >/= 150% of IBW, in which case adjusted body weight will be used.; FTBI is performed on day -7 through day -4. The total dose of radiation is 1,320 cGy.
Other intervention name(s): Busulfex®; Etoposide (VP-16; Vepesid(R) brand only)
Intervention MeSH terms: Cyclophosphamide; Busulfan; Etoposide
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: refractory multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; recurrent adult acute myeloid leukemia; recurrent adult acute lymphoblastic leukemia; refractory chronic lymphocytic leukemia; chronic phase chronic myelogenous leukemia; accelerated phase chronic myelogenous leukemia; adult acute myeloid leukemia in remission; adult acute lymphoblastic leukemia in remission; polycythemia vera; primary myelofibrosis; essential thrombocythemia; refractory anemia; refractory anemia with ringed sideroblasts; refractory anemia with excess blasts; refractory anemia with excess blasts in transformation; chronic myelomonocytic leukemia; previously treated myelodysplastic syndromes; refractory cytopenia with multilineage dysplasia; chronic eosinophilic leukemia; chronic neutrophilic leukemia; atypical chronic myeloid leukemia, BCR-ABL1 negative; myelodysplastic/myeloproliferative neoplasm, unclassifiable; 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