Allogeneic Bone Marrow Transplantation Using Less Intensive Therapy
Condition: Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma; Plasma Cell Neoplasm; Myelodysplastic Syndromes
MeSH terms: Multiple Myeloma; Kidney Neoplasms; Neoplasms, Plasma Cell; Plasmacytoma; Myelodysplastic Syndromes
Intervention: anti-thymocyte globulin; cyclophosphamide; cyclosporine; fludarabine; mycophenolate mofetil; stem cell transplantation; total body irradiation; filgrastim
Intervention description: ATG dose is 15 mg/kg intravenous (IV) every 12 hours for 6 doses on days -6, -5, and -4.
Those that should/will receive ATG in the preparative regimen:
Related donor recipients who have not had exposure to combination chemotherapy in the 6 months preceding transplant should
Unrelated donor recipients who have not had exposure to combination chemotherapy in the 3 months preceding transplant will
Unrelated donor recipients who have had only a single induction cycle for the treatment of ALL/AML or MDS or CML blast crisis should
Recipients with a prior autologous transplant in the year prior to second transplant do not require ATG.; Cyclophosphamide will be given in a two hour infusion, total dose 50 mg/kg on day -6.; Patients will receive cyclosporine A (CSA) therapy beginning on day -3 maintaining a level of >200. For adults the initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours. For children < 40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours. Patients will receive CSA until day +100.; Fludarabine 30 mg/m^2/day intravenous (IV) on day -6 through day -2., total dose 150 mg/m^2 for 5 days.; Mycophenolate mofetil (MMF) 1.5 gram twice a day (BID) or if < 50 kg will be given 15 mg/kg orally(po) BID,beginning on day -3, and discontinue at day +30 or 7 days after engraftment (3 consecutive days of absolute neutrophil count (ANC) > 0.5 x 109 /L).; On day 0, if related donor, stem cells are infused via central line. If unrelated donor, marrow/PBSC is infused after arrival and processing on day 0.; The dose of TBI will be 200 cGy given in a single fraction on day -1.; Patients with white blood cell (WBC) counts < 2500 any time after stem cell infusion will be started on G-CSF support at Day +5 at a dose of 5 mcg/kg intravenously or subcutaneously (IV/SQ) daily rounded to vial size until absolute neutrophil count (ANC) > 2500 for 2 consecutive days.
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Fludarabine; Cyclosporins; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 342.0
Sex: All
Maximum age: 75 Years
Healthy volunteers: No
Keywords: leukemia; lymphoma; myeloma

Summary:

      RATIONALE: A peripheral stem cell transplant may be able to replace blood-forming cells that
      were destroyed by chemotherapy and radiation therapy, or that have become cancer. Sometimes
      the transplanted cells from a donor can make an immune response against the body's normal
      cells. Giving cyclophosphamide and fludarabine together with total-body irradiation followed
      by cyclosporine and mycophenolate mofetil before the transplant may stop this from happening.

      PURPOSE: This clinical trial is studying how well giving combination chemotherapy together
      with radiation therapy followed by cyclosporine and mycophenolate mofetil works in treating
      patients who are undergoing a donor stem cell transplant for hematologic cancer, metastatic
      breast cancer, or kidney cancer.
    

Eligibility criteria:

        Inclusion Criteria:

        Standard patients will be enrolled into Arms 1-6. High risk patients (transplant with
        aplasia) will be considered separately in Arm 7.

          -  Age and Graft criteria (all patients)

               -  Patient's < or = 75 years old with a 5/6 or 6/6 related donor match are eligible.

               -  Patient's < or = 75 years who have a 7-8/8 HLA-A,B,C,DRB1 allele matched
                  unrelated volunteer marrow and/or peripheral blood stem cell (PBSC) donor match
                  are eligible.

          -  Disease Criteria (standard risk patients)

               -  Acute myelogenous leukemia

               -  Acute lymphocytic leukemia

               -  Chronic myelogenous leukemia all types except blast crisis (note treated blast
                  crisis in chronic phase is eligible).

               -  Non-Hodgkins lymphoma (NHL), Hodgkins, chronic lymphocytic leukemia, multiple
                  myeloma demonstrating chemosensitive disease

               -  Acquired bone marrow failure syndromes

               -  Myelodysplastic syndrome of all subtypes including refractory anemia (RA) or all
                  IPSS categories if severe pancytopenia, transfusion requirements not responsive
                  to therapy, or high risk cytogenetics. Blasts must be less than 5%. If >5%
                  requires therapy (induction or Hypomethylating agents) pre-transplant to decrease
                  disease burden.

               -  Renal cell cancer,

               -  Chronic myeloproliferative disorder, i.e. myelofibrosis

          -  Disease Criteria (High risk patients on Arm 7)

               -  Patients with refractory leukemia or MDS may be taken to transplant in aplasia
                  after induction or re-induction chemotherapy or radiolabeled antibody. These high
                  risk patients will be analyzed separately in Arm 7.

          -  Adequate organ function and performance status (all patients)

        Exclusion Criteria:

          -  Pregnancy or breast feeding

          -  Evidence of HIV infection or known HIV positive serology

          -  Active serious infection

          -  Congenital bone marrow failure syndrome

          -  Previous irradiation that precludes the safe administration of an additional dose of
             200 cGy of total body irradiation (TBI)

          -  Chronic myelogenous leukemia (CML) in refractory blast crisis

          -  Intermediate or high grade NHL, mantle cell NHL, and Hodgkins disease that is
             progressive on salvage therapy. Stable disease is acceptable to move forward provided
             it is non-bulky.

          -  Multiple Myeloma progressive on salvage chemotherapy.

        DONOR ELIGIBILITY

          -  Related will undergo apheresis - if donor is unable to undergo apheresis, a bone
             marrow harvest is acceptable; unrelated volunteer donors must be able to undergo bone
             marrow harvest or apheresis.

          -  All donors must be able to give informed consent.

          -  Donors weighing less than 40 kg (children) will need evaluation by a pediatrician for
             suitability of the apheresis procedure. Informed consent must be obtained from parent
             or guardian as applicable for minors.