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Allogeneic Non-Myeloablative Stem Cell Transplantation Utilizing Mis-Matched Family Member Stem Cells Purged Using Campath-1H

Phase 2
17 Years
Open (Enrolling)
Lymphoma, Myeloma, Leukemia, Myelodysplasia, Solid Tumors

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Trial Information

Allogeneic Non-Myeloablative Stem Cell Transplantation Utilizing Mis-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 mismatched 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.

Inclusion Criteria:

- Patients must have their pathology reviewed and the diagnosis confirmed.

- Performance status must be CALGB PS 0, 1, or 2

- Patients must have a 3-5/6 HLA-matched related donor who is evaluated and deemed able
to provide PBPCs and/or marrow by the transplant team.

- HIV antibody negative.

- Patients must test negative serum beta-HCG and must agree to use some form of
adequate birth control during the periods they receive chemotherapy and any
post-chemotherapy medications related to the transplant.

- Patients must be 17 years of age or greater.

- Patients must also have a resting MUGA and/or ECHO and PFTs with DLCO performed
before transplant and found to be acceptable according to the treating institution's
guidelines. The required minimum standards include MUGA and/or ECHO showing an EF of
40% and PFTs showing DLCO of 40%. Those with an EF 40-50%, undergo cardiac evaluation
and consultation. Also, those with DLCO 40-50%, undergo pulmonary evaluation and

- Specific populations for each disease category:

- Hematologic malignancies Those with high risk or relapsed hematologic malignancy
(including myeloid and lymphoid leukemias and lymphomas, myeloma or myelomatous
like diseases, myeloproliferative disease, myelodysplasia). Those with good risk
disease (first remission AML with inv 16 M4 Eos, M3 AML with t(15;17); or
t(8;21) in first remission are not eligible).

- Bone marrow failure:

- Those specifically with idiopathic or secondary moderate, severe or very
severe aplastic anemia (idiopathic or secondary) according to the accepted
'Camitta criteria' would be candidates.

- Those with diseases known to lead to severe marrow failure are eligible as
well. These include those with myelofibrosis or PNH.

- Solid Tumors:

- Patients must have had a biopsy confirming disease recurrence (metastases)
at some point in their history, unless the patient presented with
metastatic disease, in which case the initial primary site biopsy is

- Patients with renal cell cancer, or melanoma will be eligible for this approach at
this time. Patients will have had documented metastatic disease at some time in the
past. Patients who are in remission or with residual disease after prior therapy for
their metastatic disease are eligible, as there is no accepted cure for these
patients with metastatic disease.

- Breast Cancer- Patients will have had documented metastatic disease at some time in
the past. Patients who are in remission or with residual disease after prior therapy
for their metastatic disease are eligible. Patient must have failed at least one
chemotherapy regimen for their metastatic disease and 1 hormonal agent if they are
receptor positive.

Exclusion Criteria:

- Pregnant or lactating women,

- Patients with other major medical or psychiatric illnesses which the treating
physician feels could seriously compromise tolerance to this protocol, and

- Leukemia patients in first remission with good risk cytogenetics for leukemia
[t(15;17); t(8,22)]

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

7 years

Safety Issue:


Principal Investigator

David Rizzieri, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University Health System


United States: Food and Drug Administration

Study ID:




Start Date:

February 2003

Completion Date:

February 2015

Related Keywords:

  • Lymphoma
  • Myeloma
  • Leukemia
  • Myelodysplasia
  • Solid Tumors
  • Allogeneic Stem Cell Transplantation, Campath, HLA-Matched
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Preleukemia



Duke University Health Systems Durham, North Carolina  27710