ALL, AML, CML, Hematologic Malignancy, Hodgkin's Lymphoma, Multiple Myeloma, NHL
Conditions
Keywords
stem cell transplant, graft versus host disease, GVHD, CD+8 T cell depletion
Brief summary
The purpose of this trial is to determine if selectively removing only a small subset of T cells, called CD8+ T cells, is safe and if it can reduce the risk of graft versus host disease (GVHD) without losing the anti-cancer effects.
Detailed description
* The patient will be admitted to the hospital once a good donor is found for chemotherapy and stem cell transplant. The patient will remain in the hospital for 8 days and will receive two chemotherapy drugs (fludarabine and Busulfex) intravenously once each day for 4 days. * On the third day after the patient has finished chemotherapy, the donor cells should arrive at Dana-Farber Cancer Institute and the lab will remove CD8 cells. Then the product will be given to the patient through a central line. If there are not enough stem cells in the donor product, then the CD8 cells will not be taken out, and the patient will get the whole product. * Just before and after the transplant, the patient will also take tacrolimus and methotrexate to help prevent GVHD. Tacrolimus is a pill that will be taken orally two times a day. Methotrexate is a chemotherapy drug that is given intravenously on days 1, 3 and 6 after the transplant. In addition to the these drugs, participants will also take antibiotics to prevent infection and Filgrastim (G-CSF, neupogen) until their white blood cell counts are better. * After the stem cell infusion, check-ups and blood tests will be performed at least once a week for 1 month. At about one month, a bone marrow biopsy to look for the donor's cells in the participants bone marrow will be performed. After the 1-month evaluation, the patient will be seen at least every 2 weeks with another bone marrow biopsy at 3-4 months after the transplant. * After the patient is past 100 days since transplant, they will be followed in the clinic and have blood work done at least once a month until 6 months post transplant. * The trial will end at 6 months after the transplant, but patients will be tracked for the rest of their life to look at long-term effects of this transplant.
Interventions
DEVICECD+8 T cell depletion
CD8 depleted product Given through central line after treatment with fludarabine and busulfex intravenously for 4 days
Sponsors
Brigham and Women's Hospital
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hematologic malignancies that are candidates for allogeneic non-myeloablative stem cell transplantation * AML or ALL in first or subsequent remission, or in resistant or untreated relapse with marrow blast \< 20% of cellularity * CML in first or subsequent chronic phase, or accelerated phase * Myelodysplastic syndrome with \< 20% marrow blasts * NHL or Hodgkin's lymphoma in second or greater remission, or partial remission after salvage therapy, and in patients with marrow involvement, \<20% involvement in BM * CLL RAI stage 2-4, which has progressed after initial fludarabine containing therapy, and BM involvement of \< 20% * Multiple myeloma stage II-III, in first or subsequent plateau phase with \<20% BM plasma cells * Available unrelated donor who is fully HLA matched at HLA-A,B,C and DRB1 * Age 18 or greater * Performance status 0-2 * Life expectancy of \> 100 days * No HLA-matched related donor available
Exclusion criteria
* Myeloproliferative disorders other than CML * MDS with myeloproliferative features, or CMML * High grade Burkitts or Burkitts-like Non-Hodgkin's lymphoma * Prior allogeneic stem cell transplant * Active CNS involvement with disease * Uncontrolled infection * Pregnancy * Evidence of HIV infection * Heart failure uncontrolled my medications * Total bilirubin \> 2.0 mg/dl that is due to hepatocellular dysfunction * AST \> 2 x institutional upper limit of normal * Serum creatinine \> 2.0 mg/dl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the initial engraftment of HLA matched unrelated donor mobilized peripheral blood stem cells depleted of CD+8 cells. | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| To assess sustained engraftment | 2 years |
| to determine the incidence of GVHD | 2 years |
| to assess disease relapse. | 2 years |
Countries
United States
Outcome results
None listed