Allo-HCT MUD for Non-malignant Red Blood Cell (RBC) Disorders: Sickle Cell, Thal, and DBA: Reduced Intensity Conditioning, Co-tx MSCs
| Status: | Completed |
|---|---|
| Conditions: | Anemia, Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 1 - 25 |
| Updated: | 8/8/2018 |
| Start Date: | March 2009 |
| End Date: | August 2013 |
Pilot Study MUD HCT:Pts High Risk Sickle Cell,Other Non-Malignant RBC Disorders- Reduced Intensity Preparative Regimen, HAPLO-Identical Mesenchymal Stromal Cells
The main purpose of this project is to cure patients with high risk Sickle cell disease and
other red cell disorders including thalassemia and diamond-blackfan anemia by bone marrow
transplantation. The patients enrolled in this study will be those who lack matched sibling
donors and therefore have no other option but to undergo bone marrow transplantation using
matched but unrelated bone marrow or umbilical cord blood from the national marrow donor
program registry. Since bone marrow transplantation for these disorders using matched
unrelated donors has two major problems i.e. engraftment, or , the process of new marrow
being accepted and allowed to grow in the the patient; and graft-versus-host disease, or the
process where the new marrow "rejects" the host or the patient, this study has been devised
with methods to overcome these two problems and thus make transplantation from unrelated
donors both successful in terms of engraftment and safe in terms of side effects, both acute
and long term.
In order to accomplish these two goals, two important things will be done. Firstly, patients
will get three medicines which are considered reduced intensity because they are not known to
cause the serious organ damage seen with conventional chemotherapy. These medicines, however,
do cause intense immune suppression so these can cause increased infections. Secondly, in
addition to transplantation of bone marrow from unrelated donors, patients will also
transplanted with mesenchymal stromal cells derived from the bone marrow of their parents.
Mesenchymal stromal cells are adult stem cells that are normally found in the bone marrow and
are thought to create the right background for the blood cells to grow. They have been shown
in many animal and human studies to improve engraftment. In addition, they have a special
property by which they prevent and are now even considered to treat graft versus host
disease. Therefore, by using a reduced intensity chemotherapy regimen before transplant and
transplanting mesenchymal stromal cells, we hope to improve engraftment while at the same
time decrease the potential for severe side effects associated with a conventional transplant
which uses extremely high doses of chemotherapy.
other red cell disorders including thalassemia and diamond-blackfan anemia by bone marrow
transplantation. The patients enrolled in this study will be those who lack matched sibling
donors and therefore have no other option but to undergo bone marrow transplantation using
matched but unrelated bone marrow or umbilical cord blood from the national marrow donor
program registry. Since bone marrow transplantation for these disorders using matched
unrelated donors has two major problems i.e. engraftment, or , the process of new marrow
being accepted and allowed to grow in the the patient; and graft-versus-host disease, or the
process where the new marrow "rejects" the host or the patient, this study has been devised
with methods to overcome these two problems and thus make transplantation from unrelated
donors both successful in terms of engraftment and safe in terms of side effects, both acute
and long term.
In order to accomplish these two goals, two important things will be done. Firstly, patients
will get three medicines which are considered reduced intensity because they are not known to
cause the serious organ damage seen with conventional chemotherapy. These medicines, however,
do cause intense immune suppression so these can cause increased infections. Secondly, in
addition to transplantation of bone marrow from unrelated donors, patients will also
transplanted with mesenchymal stromal cells derived from the bone marrow of their parents.
Mesenchymal stromal cells are adult stem cells that are normally found in the bone marrow and
are thought to create the right background for the blood cells to grow. They have been shown
in many animal and human studies to improve engraftment. In addition, they have a special
property by which they prevent and are now even considered to treat graft versus host
disease. Therefore, by using a reduced intensity chemotherapy regimen before transplant and
transplanting mesenchymal stromal cells, we hope to improve engraftment while at the same
time decrease the potential for severe side effects associated with a conventional transplant
which uses extremely high doses of chemotherapy.
Inclusion Criteria:
- Patients with sickle cell disease (SCD) 1-25 years of age with an HLA-identical, but
unrelated, donor or 1 human leukocyte antigen (HLA) allele mismatched bone marrow or
up to 2 HLA antigen mismatched umbilical cord blood (UCB) donor with one or more of
the following:
- Stroke, central nervous system (CNS) hemorrhage or a neurologic event lasting
longer than 24 hours.
- Acute chest syndrome with a history of recurrent hospitalizations or exchange
transfusions.
- Recurrent vaso-occlusive pain, 3 or more episodes per year for 3 years or more
years; or recurrent priapism.
- Impaired neuropsychological function and/or abnormal cerebral MRI scan or
abnormal transcranial Doppler (TCD).
- Stage I or II sickle lung disease.
- Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration
rate (GFR) 30-50% of the predicted normal value).
- Bilateral proliferative retinopathy and major visual impairment in at least one
eye.
- Osteonecrosis of multiple joints with documented destructive changes.
- Requirement for chronic transfusions but with RBC alloimmunization >2 antibodies
during long term transfusion therapy.
- Failure of hydroxyurea (HU) therapy.
- Patients aged 0-21 years with transfusion dependent alpha- or beta-thalassemia who
have an HLA-identical or 1 HLA allele mismatched bone marrow or up to 2 HLA mismatched
UCB donor.
- Patients aged 0-21 years with Diamond-Blackfan anemia who have an HLA-identical or 1
HLA allele mismatched bone marrow or up to 2 HLA mismatched UCB donor. Diamond-
Blackfan anemia patients will only be eligible if they have failed steroid therapy.
Exclusion Criteria:
- Patients with one or more of the following:
- Karnofsky or Lansky performance score <70 (See Appendices I and II).
- Stage III-IV lung disease (Appendix III).
- GFR<30% predicted normal values.
- Pregnant or lactating females.
- Active serious infection whereby patient has been on intravenous antibiotics for
one week prior to study entry.
- Any patient with AIDS or HIV seropositivity.
- Any patient with invasive aspergillus infection within one year of study entry.
- Psychologically incapable of undergoing bone marrow transplant (BMT) with
associated strict isolation or documented history of medical non-compliance.
We found this trial at
2
sites
Children's Hospital of Alabama Children
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Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
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