Phase II Trial of a Chemotherapy Alone Regimen of IV Busulfan (Busulfex), Melphalan and Fludarabine as Myeloablative Regimen Followed by an Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplant From an HLA-Identical, or HLA-Non Identical Related or Unrelated Donor
Condition: Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Allogeneic Marrow Transplant
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Preleukemia; Myelodysplastic Syndromes
Intervention: BUSULFAN, MELPHALAN, FLUDARABINE, G-CSF; BUSULFAN, MELPHALAN, FLUDARABINE, G-CSF; BUSULFAN, MELPHALAN, FLUDARABINE, G-CSF
Intervention description: All research participants will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.8- 1.0 mg/Kg/dose Q6H x 10 doses), melphalan (70 mg/m2/dose x 2 doses) and fludarabine (25 mg/m2/day x 5 doses). Doses of busulfan will be adjusted according to plasma levels. All research participants will also receive ATG (thymoglobulin®) prior to transplant to promote engraftment.All research participants will also receive G-CSF posttransplant to foster engraftment.
The preferred source of stem cells will be peripheral blood stem cells (PBSC) induced and mobilized by treatment of the donor with G-CSF for 5-6 days. PBSC obtained through 2-3 leukaphereses will be Isolex® 300i separated CD34+ stem cell column selected and E-rosette depleted (E-). The CD34+Eperipheral blood progenitors will be administered to the research participants after they have completed cytoreduction.; All research participants will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.8- 1.0 mg/Kg/dose Q6H x 10 doses), melphalan (70 mg/m2/dose x 2 doses) and fludarabine (25mg/m2/day x 5 doses). Doses of busulfan will be adjusted according to plasma levels. All research participants will also receive ATG (Thymoglobulin®) prior to transplant to promote engraftment. No drug prophylaxis against GvHD will be administered post transplant. All research participants will also receive G-CSF posttransplant to foster engraftment.
The preferred source of stem cells will be peripheral blood stem cells (PBSC) induced and mobilized by treatment of the donor with G-CSF for 5-6 days. PBSC obtained through 2-3 leukaphereses will be Isolex® 300i separated CD34+ stem cell column selected and E-rosette depleted (E-). The CD34+Eperipheral blood progenitors will be administered to the research participants after they have completed cytoreduction.; All research participants will be conditioned for transplantation with intravenous busulfan (busulfex®) (0.8- 1.0 mg/Kg/dose Q6H x 10 doses), melphalan (70 mg/m2/dose x 2 doses) and fludarabine (25mg/m2/day x 5 doses). Doses of busulfan will be adjusted according to plasma levels. All research participants will also receive ATG (Thymoglobulin®) prior to transplant to promote engraftment. No drug prophylaxis against GvHD will be administered post transplant. All research participants will also receive G-CSF posttransplant to foster engraftment.
The preferred source of stem cells will be peripheral blood stem cells (PBSC) induced and mobilized by treatment of the donor with G-CSF for 5-6 days. PBSC obtained through 2-3 leukaphereses will be Isolex® 300i separated CD34+ stem cell column selected and E-rosette depleted (E-). The CD34+Eperipheral blood progenitors will be administered to the research participants after they have completed cytoreduction.
Intervention MeSH terms: Vidarabine; Fludarabine; Fludarabine phosphate; Melphalan; Busulfan; Lenograstim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 96.0
Sex: All
Maximum age: 54 Years
Healthy volunteers: No
Keywords: Cancer; Donors; Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Lymphoma; AML; ALL; CML; Allogeneic marrow transplant; Bone marrow transplant

Summary:

      The purpose of this research study is:(1) to determine if high doses of chemotherapy without
      total body irradiation can allow selected stem cells to take and grow,(2) to determine if
      selected stem cells from the blood or marrow can take and not cause a complication called
      graft-versus-host disease (GvHD) and (3) to evaluate the side effects of the combination of
      chemotherapy drugs used for these transplants. In the last 10 years we have developed
      chemotherapy combinations to be used for this T-cell depleted transplant protocol. By using
      three chemotherapy drugs (IV busulfan, melphalan and fludarabine), we hope to have a good
      chemotherapy combination to kill cancer cells, and to make the graft take, without the side
      effects of total body irradiation. The chemotherapy drugs to be tested in this protocol are
      busulfan, melphalan and fludarabine, all of which have been used successfully for stem cell
      transplantation, but not given together as in this specific regimen. This is what is being
      tested in this study.

      Our initial trials in the 1980's with T-cell depleted transplants showed less GvHD, but the
      overall results of the transplants were not better. The reason for this was that the stem
      cells did not take and engraft in 15% of our adult patients. This failure of the stem cells
      to take can leave patients without bone marrow or blood cells necessary for life. Most stem
      cell transplants were done using bone marrow (BMA) obtained from the donors. However, if we
      give a medication called G-CSF by shots to the donor, we can collect peripheral blood stem
      cells (PBSC) and use them for transplant. The advantage of this approach is that we can
      collect 2-20 times more stem cells than that obtained from the marrow. It has been proven
      that a larger number of stem cells in the graft make it more difficult for the patient to
      reject the stem cells. Some donors may be too small to provide peripheral blood stem cells or
      they may not want to take G-CSF shots. In these cases the donors will have their marrow
      collected in the operating room under general anesthesia.

      Stem cell transplants can lead to a condition known as acute graft-versus-host disease or
      GvHD. This disease is caused by an assault by certain cells in the marrow or blood (T-cells)
      of the donor (graft) against your body (the host). These T-cells see your body as foreign and
      attack it. The disease causes a skin rash, liver disease, and diarrhea. Methods were
      developed at this institution to prevent GvHD. These methods take out most of the T-cells
      (responsible for GvHD) from the marrow or blood stem cells before transplant. This is called
      "T-cell depletion" or "stem cell selection". In this hospital, we use two types of methods of
      T-cell depletion: one method is used with peripheral blood stem cells and one for bone
      marrow. Both these techniques have been successful in preventing both acute and chronic GvHD.
      You will receive a T-cell depleted stem cell transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis: Acute myelogenous leukemia (AML) Acute undifferentiated leukemia (AUL);
             Acute lymphoblastic leukemia (ALL); Acute biphenotypic leukemia (AbiL); Chronic
             myelogenous leukemia (CML); Non Hodgkin's lymphoma (NHL); Myelodysplastic syndrome
             (MDS) Aplastic anemia (AA)

          -  Status: CR1 first remission; CR2 second remission; CP chronic phase

          -  HLA-matched Related donors: Research participants who have an HLA-matched related
             donor are eligible for entry on this protocol. This will include a healthy related
             donor who is genotypically or phenotypically matched at all A, B and DRB1 loci, as
             tested by DNA analysis.

          -  HLA-compatible Unrelated donors: Research participants who do not have a related
             HLA-matched donor but have an unrelated donor who is either matched at all A, B and
             DRB1 loci or who is mismatched at 1/6 loci (A, B, or DRB1) as tested by DNA analysis,
             will be eligible for entry on this protocol.

          -  HLA-mismatched Related donors: Research participants who do not have a related or
             unrelated HLA-compatible donor must have a healthy family member who is at least
             HLA-haplotype identical to the recipient.

          -  Research participants must have a healthy HLA compatible related or unrelated donor
             who is willing to receive G-CSF injections and undergo apheresis for PBSC collection,
             or undergo a marrow harvesting procedure.

          -  Research participants should be < 55 years. There is no lower age limit. Research
             participants > 55 years will be accrued on a case by case basis after discussion and
             approval by the BMT Service.

          -  Research participants may be of either gender or any ethnic background.

          -  Research participants must have a Karnofsky (adult) or Lansky (pediatric) Performance
             Status > 70%

          -  Research participants must have adequate physical function

        Exclusion Criteria:

          -  Active CNS or skin leukemic/lymphomatous involvement

          -  Female research participants who are pregnant or breast-feeding

          -  Active viral, bacterial or fungal infection

          -  Research participant seropositive for HIV-I/II; HTLV -I/II

          -  Research participants who have undergone a prior allogeneic or autologous stem cell
             transplant within the previous six months.