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 Rel

• Status: Completed
• Trial end date: 2009-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Memorial Sloan Kettering Cancer Center
• Treatments: Busulfan; Fludarabine; Fludarabine phosphate; Lenograstim; Melphalan; Vidarabine

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.