Clinical Trial: Improving the Results of Bone Marrow Transplantation for Patients With Severe Congenital Anemias
Study Status: RECRUITING
Recruit Status: RECRUITING
Study Type: INTERVENTIONAL
Official Title: Nonmyeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Severe Congenital Anemias Including Sickle Cell Disease (SCD) and B-Thalassemia
Brief Summary:
People with severe congenital anemias, such as sickle cell anemia and beta-thalassemia, have been cured with bone marrow transplantation (BMT).
The procedure, however, is limited to children younger than the age of 16 because the risks are lower for children than for adults.
The purpose of this study is to explore the use of a BMT regimen that, instead of chemotherapy, uses a low dose of radiation, combined with two immunosuppressive drugs.
This type BMT procedure is described as nonmyeloablative, meaning that it does not destroy the patient s bone marrow.
It is hoped that this type of BMT will be safe for patients normally excluded from the procedure because of their age and other reasons.
To participate in this study, patients must be between the ages of 18 and 65 and have a sibling who is a well-matched stem-cell donor.
Beyond the standard BMT protocol, study participants will undergo additional procedures.
The donor will receive G-CSF by injection for five days; then his or her stem cells will be collected and frozen one month prior to BMT.
Approximately one month later, the patient will be given two immune-suppressing drugs, Campath 1-H and Sirolimus, as well as a single low dose of total body irradiation and then the cells from the donor will be infused.
Prior to their participation in this study, patients will undergo the following evaluations: a physical exam, blood work, breathing tests, heart-function tests, chest and sinus x-rays, and bone-marrow sampling.
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Detailed Summary:
Nonmyeloablative allogeneic peripheral blood stem cell (PBSC) transplants are currently being investigated in phase I/II trials assessing engraftment, efficacy, and toxicity at a number of transplant centers.
Preliminary data have shown a high rate of complete donor engraftment with a relatively low toxicity profile.
The decreased risk of transplant-related complications associated with nonmyeloablative transplants expands eligibility to patients with nonmalignant hematological disorders curable by allogeneic transplantation; however, significant toxicity with current regimens persists including severe graft versus host disease (GVHD) leading to significant morbidity and mortality.
Moreover, mixed chimerism has been shown to be sufficient to induce clinical remissions in children with nonmalignant hematologic disorders undergoing conventional allogeneic transplantation.
Therefore, newer regimens need to be developed that are more applicable to patients with non-malignant disorders in whom no graft vs. leukemia effect is needed, and where mixed chimerism is sufficient for disease amelioration.
In this protocol, we propose transplantation in patients with severe beta-globin disorders including sickle cell disease (SCD), and beta-thalassemia, considered at high risk for complications from or ineligible for standard BMT, with allogeneic PBSCs from an HLA identical sibling using a novel immunosuppressive regimen without myeloablation in an attempt to further decrease the transplant related morbidity/mortality.
The low intensity nonmyeloablative conditioning regimen will consist of low dose radiation, Alemtuzumab (Campath ) and Sirolimus (Rapamune ) as a strategy to provide adequate immunosuppression to allow sufficient engraftment for clinical remission with a lower risk of GVHD development.
T-cell replete, donor-derived, granulocyte colony stimulating factor (filgrastim, G-CSF) mobilized PBSCs will be used to establish hematopoietic and lymphoid reconstitution.
The primary endpoint of this study is treatment success at one year, defined as full donor type hemoglobin on hemoglobin electrophoresis for patients with SCD and transfusion-independence for patients with beta-thalassemia.
Other end points include degree of donor-host chimerism necessary for long-term graft survival and disease amelioration, incidence of acute and chronic graft-vs-host disease (GVHD), incidence of graft rejection, transplant related morbidity, as well as disease-free and overall survival.
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Current Primary Outcome: This trial is designed to estimate treatment success, which is anticipated to be about 80%.
The study started with a sample size of 25 and this will allow us to estimate the success of engraftment.
For example, if the estimated rate is .80, the 95% confidence interval would be approximately (.64, .96).
This would allow us to rule out rate of treatment success of less than .64.
If the estimated rate is .70, the 95% confidence interval would be approximately (.52, .88)
and we could rule out rate of treatment success below .50.
If the lower bound of the 95% confidence interval is raised to 0.7, the number of subjects needed to accrue with respect to success rate is listed below.
Original Primary Outcome: This trial is designed to estimate treatment success, which is anticipated to be about 80%.
The study started with a sample size of 25 and this will allow us to estimate the success of engraftment.
For example, if the estimated rate is .80, the 95% confidence interval would be approximately (.64, .96).
This would allow us to rule out rate of treatment success of less than .64.
If the estimated rate is .70, the 95% confidence interval would be approximately (.52, .88)
and we could rule out rate of treatment success below .50.
If the lower bound of the 95% confidence interval is raised to 0.7, the number of subjects needed to accrue with respect to success rate is listed below.
Current Secondary Outcome:
Original Secondary Outcome:
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: May 29, 2003
Date Started: July 16, 2004
Date Completion: January 20, 2024
Last Updated: July 06, 2023
Last Verified: July 01, 2023
