Busulfan, Melphalan, Fludarabine and T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Followed by Post Transplantation Donor Lymphocyte Infusions
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      The patients are being offered a stem cell transplant. Stem cells are very early blood cells.
      They have not yet matured to become red or white blood cells or platelets. They have already
      received the standard treatment of chemotherapy and an autologous stem cell transplant. An
      autologous stem cell transplant is when the patient receives their infusion of their own
      cells. Thi will give the patient a better chance of curing the disease, this protocol
      includes an infusion of stem cells from the blood (or the bone marrow) of another person.
      This is called an allogeneic stem cell transplant. The stem cells will begin to grow in the
      bone marrow and produce new blood cells.

      Allogeneic stem cell transplants can cause a condition called graft-versus-host disease or
      GVHD. In GVHD, a kind of white blood cell from the donor (graft) begins to attack the body
      (host). That blood cell is called a T-cell. It is a cell that normally helps to protects
      against things like bacteria and viruses. In this case, the donor's T-cells see the body as
      foreign in the same way they would see bacteria as foreign. GVHD can be fatal. In order to
      lower the chance that the patient will get GVHD this protocol treatment will remove the
      T-cells from the donor's cells. This is called T-cell depletion. The T cells are removed by a
      system called "Clinimacs". This method is still being evaluated through clinical trials and
      not been approved by the Federal Drug Administration (FDA) at this time.

      Before the transplant, the physician will treat the bone marrow to get rid of the cancer. The
      physician uses three chemotherapy drugs plus ATG. The chemotherapy drugs (Busulfan, Melphalan
      and Fludarabine) kills the cancer. ATG gets rid of any of the patients T cells that survive
      the chemotherapy. This ensures that the donor stem cells are not rejected. The patient will
      also receive additional white blood cells called lymphocytes from the donor. This is called a
      donor lymphocyte infusion or DLI. These additional infusions will help cause a
      graft-versus-myeloma effect and can help the donor stem cells grow.
    


Intervention name(s): busulfan, melphalan and fludarabine; busulfan, melphalan and fludarabine
Intervention type(s): Drug; Drug
Intervention description(s): Patients will be cytoreduced with IV busulfan, melphalan and fludarabine. Busulfan will be administered at a dose of 0.8mg/Kg q6hrs for 10 doses on days -9, -8, -7. Doses for busulfan should be adjusted according to pharmacokinetic studies. Melphalan will be administered at a dose of 70 mg/m2/day for 2 days on days -7, -6. Fludarabine will be administered at a dose of 25 mg/m2/day for 5 days on days -6, -5, -4, -3, -2. Patients will also receive rabbit anti-thymocyte globulin (ATG) to prevent immune mediated graft rejection. The ATG will be administered at a dose of 2.5 mg/Kg/day IV on days -3 and -2. Doses for busulfan, melphalan and ATG should be adjusted if patient is > 125% ideal body weight and should be calculated on adjusted ideal body weight.; Patients will be cytoreduced with IV busulfan, melphalan and fludarabine. Busulfan will be administered at a dose of 0.8mg/Kg q6hrs for 10 doses on days -9, -8, -7. Doses for busulfan should be adjusted according to pharmacokinetic studies. Melphalan will be administered at a dose of 70 mg/m2/day for 2 days on days -7, -6. Fludarabine will be administered at a dose of 25 mg/m2/day for 5 days on days -6, -5, -4, -3, -2. Patients will also receive rabbit anti-thymocyte globulin (ATG) to prevent immune mediated graft rejection. The ATG will be administered at a dose of 2.5 mg/Kg/day IV on days -3 and -2. Doses for busulfan, melphalan and ATG should be adjusted if patient is > 125% ideal body weight and should be calculated on adjusted ideal body weight.
Other intervention name(s): Doses of fludarabine should be reduced to 80% of dose for measured creatinine; clearance of 40-70ml/min. Day - 1 will be a day of rest before receiving the; T-cell depleted stem cell product on day 0. The preferred stem cell product; will be peripheral blood stem cells but if the donor is unable or unwilling to; donate peripheral blood stem cells, bone marrow will be used as the stem cell; source. Patients will receive post-transplant G-CSF starting on day +7.; Doses of fludarabine should be reduced to 80% of dose for measured creatinine; clearance of 40-70ml/min. Day - 1 will be a day of rest before receiving the; T-cell depleted stem cell product on day 0. The preferred stem cell product; will be peripheral blood stem cells but if the donor is unable or unwilling; to donate peripheral blood stem cells, bone marrow will be used as the stem cell; source. Patients will receive post-transplant G-CSF starting on day +7.
Intervention MeSH terms: Vidarabine; Fludarabine; Fludarabine phosphate; Melphalan; Busulfan; Lenograstim
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Myeloma; Busulfan; Melphalan; Fludarabine; T-Cell; Stem Cell Transplantation; 10-051