Stem Cell Transplant for Sickle Cell Disease (Sickle-AID Trial)
Palo Alto (17 mi)Age: < 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Calgary
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The aim of this study to evaluate the safety and efficacy of a nonmyeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with sickle cell disease (SCD) who have a matched related major ABO-incompatible donor. The nonmyeloablative regimen will use alemtuzumab, total body irradiation (TBI) and sirolimus for immune suppression. This study will expand the access of HSCT for patients with SCD who are currently not eligible because of donor restrictions.
Is the drug combination of Alemtuzumab, Sirolimus, and Total Body Irradiation a promising treatment for Sickle Cell Disease?Yes, the drug combination of Alemtuzumab, Sirolimus, and Total Body Irradiation shows promise for treating Sickle Cell Disease. In a study with children and adolescents, this treatment led to successful stem cell transplants without sickling crises, and all patients survived without major complications. This suggests it could be an effective option for managing the disease.12378
What safety data exists for stem cell transplant in sickle cell disease using Alemtuzumab and related treatments?Alemtuzumab (Campath) is used in hematopoietic cell transplantation to prevent graft-versus-host disease, but it can cause delayed immune reconstitution, viral reactivations, and leukemia relapse. There are reports of acute renal failure and disseminated intravascular coagulation following its use. In a study involving children with sickle cell disease, a regimen including alemtuzumab, total body irradiation, and sirolimus showed no graft failure or GVHD, with 100% event-free and overall survival rates over a median follow-up of 19.5 months. However, long-term safety and efficacy require further study.25678
What data supports the idea that Stem Cell Transplant for Sickle Cell Disease is an effective treatment?The available research shows that Stem Cell Transplant for Sickle Cell Disease, using a nonmyeloablative regimen with alemtuzumab and total body irradiation, has been effective in children and adolescents. In a study with 16 patients, all achieved successful engraftment, meaning the new stem cells started working in their bodies. Importantly, there were no sickling crises after the transplant, and all patients survived without major complications over a median follow-up of 19.5 months. This suggests that the treatment can be very effective in managing Sickle Cell Disease.23478
Do I have to stop taking my current medications for the trial?The protocol does not specify if you need to stop taking your current medications. However, since the trial involves immune suppression with sirolimus, you should discuss your current medications with the study team to ensure there are no interactions.
Eligibility Criteria
This trial is for children with sickle cell disease aged 1 to less than 19 years who have had complications like pain crises, stroke, or organ damage despite treatment. They must be eligible for a stem cell transplant and have a related donor who doesn't match their blood type.Inclusion Criteria
I have sickle cell disease, confirmed by a specific blood test.
I am between 12 and 18 years old.
Treatment Details
The study tests a nonmyeloablative transplant approach using alemtuzumab (an antibody), low-dose total body irradiation, and sirolimus (for immune suppression) in pediatric patients with SCD having ABO-incompatible donors.
1Treatment groups
Experimental Treatment
Group I: Non-myeloablative conditioningExperimental Treatment3 Interventions
Non-myeloablative conditioning
Alemtuzumab is already approved in United States, European Union, European Union for the following indications:
🇺🇸 Approved in United States as Campath for:
- Chronic lymphocytic leukemia
- Multiple sclerosis
🇪🇺 Approved in European Union as Lemtrada for:
- Multiple sclerosis
🇪🇺 Approved in European Union as Campath for:
- Chronic lymphocytic leukemia
Find a clinic near you
Research locations nearbySelect from list below to view details:
Alberta Children's HospitalCalgary, Canada
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Who is running the clinical trial?
University of CalgaryLead Sponsor
References
Alemtuzumab in stem cell transplantation. [2021]Alemtuzumab, otherwise called CAMPATH-1H, is a humanized monoclonal antibody directed against the CD52 antigen of lymphocytes. It is one of a family of CAMPATH-1 antibodies that have been used over the last 20 yr in stem cell transplantation for depletion of donor and recipient T-cells to prevent graft-versus-host disease and graft rejection. Clinical trials have been carried out by a cooperative group of physicians and the protocols have gradually evolved as different problems have been identified and overcome. T-cell depletion carries risks of reducing graft-versus-tumor effects and increasing susceptibility to virus reactivation, but offers significant benefits in terms of reduced mortality and morbidity from graft-versus-host disease (GVHD). Two protocols are currently favored: (1) simple addition of CAMPATH-1H to the stem cell infusion and (2) administration in vivo prior to the transplant--especially in the context of nonmyeloablative conditioning regimens. Both of these give excellent control of GVHD with minimal graft rejection. Contrary to earlier expectations, a short course of posttransplant cyclosporin A (CyA) appears to further reduce transplant-related mortality, mainly by a reduction in late deaths from infection. These results need to be consolidated by means of prospective clinical trials.
Acute renal failure and disseminated intravascular coagulation following an idiosyncratic reaction to Alemtuzumab (Campath 1H) or fludarabine. [2017]Alemtuzumab (Campath 1H) is a recombinant DNA derived humanized monoclonal antibody which targets CD52 antigens on B and T cells. It is increasingly used as a conditioning agent for bone marrow transplantation. We describe the case of a 37 year old woman who developed acute renal failure and disseminated intravascular coagulation (DIC) following one dose of Campath and Fludarabine. Campath was thought to be the most likely causal agent although Fludarabine alone or in combination with Campath cannot be excluded. Despite there being many documented side effects of Campath there are currently no reports in the literature of acute renal failure and DIC. The transplant had to be aborted and 9 months on the patient is still requiring dialysis twice a week.
CAMPATH: from concept to clinic. [2018]Lymphocyte depletion has a long history in the area of therapeutic immunosuppression. CAMPATH-1H (alemtuzumab) was generated in an attempt to replace anti-lymphocyte globulins in the transplant arena. Its efficacy in killing lymphocytes has established it as a licensed drug for the management of chronic lymphocyte leukaemia. Short-term therapy with alemtuzumab has demonstrated long-term benefit in a number of autoimmune conditions. This drug has the potential to facilitate recruitment of tolerance processes so enabling drug minimization in transplantation, autoimmune and hypersensitivity diseases.
Alemtuzumab in allogeneic hematopoetic stem cell transplantation. [2021]With the use of reduced-intensity conditioning (RIC), early toxicity of allogeneic stem cell transplantation (SCT) has been much reduced. Graft-versus-host disease (GvHD) causes morbidities and mortality. Alemtuzumab is a mAb directed against CD52. When administered prior to transplant, it leads to T-cell depletion. Incorporation of alemtuzumab in RIC results in low rates of GvHD and treatment-related mortality (TRM) in haematological diseases, even in the setting of mismatched-donor transplantation.
Alemtuzumab induction in deceased donor kidney transplantation. [2017]Alemtuzumab (Campath-1H), a humanized monoclonal antibody directed against CD52, is a lymphocyte-depleting agent currently being evaluated as an induction agent in solid organ transplantation. This study analyzed the clinical outcomes and effects on peripheral blood lymphocyte subset counts in adult deceased donor renal transplant recipients who received an alemtuzumab-based induction protocol.
Use of the ImmuKnow assay to evaluate the effect of alemtuzumab-depleting induction therapy on cell-mediated immune function after renal transplantation. [2021]Good outcomes after renal transplantation are dependent on effective immunosuppression while minimizing infection. Alemtuzumab (Campath or Campath-1H) is an anti-CD52 humanized monoclonal IgG1 antibody which induces rapid and sustained depletion of circulating lymphocytes and has been effectively used as an immunosuppressant in post-transplant induction therapy.
Nonmyeloablative Matched Sibling Donor Hematopoietic Cell Transplantation in Children and Adolescents with Sickle Cell Disease. [2020]Sickle cell disease is a potentially debilitating hemoglobinopathy associated with early mortality. The only established curative therapy is hematopoietic cell transplantation (HCT) with a matched sibling donor. The National Institutes of Health nonmyeloablative regimen of alemtuzumab/300 cGy total body irradiation and prolonged sirolimus exposure for graft-versus-host disease (GVHD) prophylaxis was administered to 16 children and adolescents. Infused products were unmanipulated granulocyte colony stimulating factor mobilized peripheral blood stem cells. All patients achieved mixed donor-recipient engraftment with no cases of secondary graft failure to date. Two patients have donor myeloid chimerism in the range of 30% to 40%. No sickling crises post-HCT have been observed. Event-free and overall survival rates are 100% with median follow-up of 19.5 months. No cases of GVHD have been observed. Sirolimus weaning was possible in all but one eligible patient to date. Ongoing follow-up and a larger prospective clinical trial are required to determine the long-term safety and efficacy of this regimen in children.
Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome. [2023]Label="BACKGROUND AND OBJECTIVE">Alemtuzumab (Campath®) is used to prevent graft-versus-host disease and graft failure following pediatric allogeneic hematopoietic cell transplantation. The main toxicity includes delayed immune reconstitution, subsequent viral reactivations, and leukemia relapse. Exposure to alemtuzumab is highly variable upon empirical milligram/kilogram dosing.