Allogeneic Non-myeloablative Stem Cell Transplantation Utilizing Matched Family Member Stem Cells Purged Using Campath-1H
Allogeneic bone marrow transplantation may cure or ameliorate illnesses of many types;
however the toxicity of the procedure limits its broad applicability. Hematologic
malignancies of all types have shown responses. Those with marrow failure, such as aplasia,
and hemoglobinopathies have further shown responses in multiple trials as well. Even
patients with certain solid tumors, such as breast, renal cell, and melanoma have shown
partial or complete responses to allogeneic therapy. The limiting effect of the historical
methods of aggressive induction for allogeneic therapy were extremely toxic, requiring
limiting those offered allogeneic therapy to the healthiest of the ill patients. Work over
the last decade has shown that less toxic agents targeting the immune system effectively
allowed engraftment with less effects on the patient's liver, lungs, and other vital organs.
We and others have completed multiple trials showing the effective use of these less toxic,
non-myeloablative, regimens for allogeneic therapy. Trials with fludarabine and
cyclophosphamide at standard doses (patients are not ablated and recover blood counts in 2
weeks) allow for 80% of patients to engraft donor cells. Some groups have added low doses
of radiation to this combination, with 80-100% allogeneic engraftment. The lessened
toxicity of this approach has been confirmed in multiple studies, including our own data
with the specific schema in this treatment plan reviewed below. Phase I results with this
combination: Our group has combined the above combination of fludarabine and
cyclophosphamide with the antibody CAMPATH 1H. This antibody is given to the patient to
purge the immune system and prevent rejection. It also purges the T cells in the donated
stem cells to minimize graft versus host disease (GVHD). This approach has been proven
successful in multiple trials using standard more toxic ablative procedures. Our approach
over the last 3 years has been very successful using this antibody with the less toxic
non-myeloablative procedure and our trials have completed. We have presented our
preliminary results, with data on long term follow up for outcomes being collected. We have
shown that 100% of patients with a malignancy or marrow failure treated with this regimen in
our early phase trial engrafted donor cells. There was only an 8% severe GVHD risk, though
the risk for infection remains high with a risk of fungal and viral infection about 5% each.
Despite working with older, more infirmed patients, only 3/40 patients died within the
first 100 days from therapy. Similar approaches on matched unrelated donors have been
reported by other groups as well. As the phase I feasibility trial is complete and the
outcomes encouraging, this protocol will follow the same general treatment plan and allow
further information to be gained for long term follow up of patients treated with this
approach.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Estimate toxicity and overall survival rates in three cohorts of patients treated with a non-myeloablative preparative regimen followed by matched related allogeneic stem cells for allogeneic transplantation.
5 years
Yes
David Rizzieri, MD
Principal Investigator
Duke University Health System
United States: Food and Drug Administration
Pro00008380
NCT00578942
May 2005
May 2014
Name | Location |
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Duke University Health Systems | Durham, North Carolina 27710 |