Back to resultsNonmyeloablative Stem Cell Transplant in Children With Sickle Cell Disease and a Major ABO-Incompatible Matched Sibling Donor (Sickle-AID)
Primary Purpose
Sickle Cell Disease, Stem Cell Transplant Complications, Red Blood Cell Disorder
Status
Recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Alemtuzumab
Total Body Irradiation
Sirolimus
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease focused on measuring sickle cell disease, stem cell transplant, red blood cell engraftment, nonmyeloablative, pure red cell aplasia
Eligibility Criteria
Inclusion Criteria:
- Patients must be ≥ 12 months and < 19 years of age at the time of study enrollment.
Patients must have sickle cell disease as defined by hemoglobin electropheresis, as follows:
- homozygous Hb S disease (HbSS),
- sickle-Hb C disease (HbSC),
- sickle beta-plus-thalassemia (HbS/β+), or
- sickle beta-null-thalassemia (HbS/βo)
Patients must meet standard eligibility criteria to undergo HSCT, including but not limited to one or more of the following:
- history of repeated (more than 1) bony (vaso-occlusive) crisis
- history of stroke
- elevated transcranial Doppler velocity not eligible for hydroxyurea, as per TWiTCH trial (ie. severe vasculopathy)
- history of acute chest crisis or splenic sequestration crisis
- history of priapism in males
- history of osteonecrosis
- pulmonary hypertension as documented by tricuspid regurgitation jet velocity (TRV) > 2.5 m/s on echocardiogram
- red cell allo-immunization (≥ 2 antibodies) during long term transfusion therapy
- Sickle complications should be present despite the use of hydroxyurea, but this is not an absolute requirement, if the treating team considers the patient to be at high risk for further crisis episodes.
Exclusion Criteria:
- Patients who are unable to comply with or follow the study protocol.
- Patients with known hypersensitivity to sirolimus, its derivatives or to any of its components.
Sites / Locations
- Alberta Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Non-myeloablative conditioning
Arm Description
Non-myeloablative conditioning
Outcomes
Primary Outcome Measures
Incidence of pure red cell aplasia (PRCA)
Clinical definition: reticulocytopenia < 10x109/L (< 1%) lasting more than 60 days after HSCT, or Pathological definition: the absence of erythroid precursors in the marrow in the setting of adequate myeloid, lymphoid and megakaryocytic precursors
Secondary Outcome Measures
RBC chimerism measured by peripheral blood flow cytometry
Peripheral blood for RBC chimerism on flow sorted erythroid precursor cells
RBC chimerism measured by bone marrow BFU-erythroid forming colonies
Bone marrow will be performed between Day +45 and +60
Primary graft failure
Measured by donor chimerism from peripheral blood and bone marrow
Secondary graft failure
Measured by donor chimerism in peripheral blood and bone marrow
Disease recurrence
Measured by peripheral blood Hb S level
Incidence and severity of acute GVHD
Acute GVHD grade will be accessed using modified CIBMTR criteria
Incidence and severity of chronic GVHD
Chronic GVHD will be accessed using the NIH consensus criteria
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03214354
Brief Title
Nonmyeloablative Stem Cell Transplant in Children With Sickle Cell Disease and a Major ABO-Incompatible Matched Sibling Donor
Acronym
Sickle-AID
Official Title
A Phase II Pilot Study of Nonmyeloablative Conditioning Hematopoietic Stem Cell Transplantation in Children With Sickle Cell Disease Who Have a Matched Related Major ABO-Incompatible Donor (Sickle-AID)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Recruiting
Study Start Date
July 5, 2017 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Calgary
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
Sickle cell disease (SCD) is a debilitating chronic blood disorder with multi-system end-organ damage that leads to morbidity and early mortality. The only cure for SCD is hematopoietic stem cell transplantation (HSCT), which given the risks with unrelated HSCT, is only an option for a minority of patients who have a matched sibling donor.
In the field of HSCT, blood group ABO incompatibility between donor and recipient is not a contraindication and several studies do not show compromised outcomes. However, in the context of nonmyeloablative (NMA) conditioning and major ABO-incompatibility, when the recipient has existing antibodies to donor red blood cells, pure red cell aplasia (PRCA) may occur.
This phase II pilot study will enroll SCD patients with a matched related major ABO-incompatible donor to determine the safety and efficacy of NMA-HSCT. Biological studies will include a plan to study and monitor red cell engraftment in this population to facilitate early detection and interventional measures to prevent and treat PRCA.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease, Stem Cell Transplant Complications, Red Blood Cell Disorder, Pure Red Cell Aplasia
Keywords
sickle cell disease, stem cell transplant, red blood cell engraftment, nonmyeloablative, pure red cell aplasia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Phase II pilot, non-randomized, prospective study to evaluate the safety and efficacy of a nonmyeloablative conditioning allogeneic stem cell transplantation for patients with sickle cell disease who have a matched related major ABO-incompatible donor.
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Non-myeloablative conditioning
Arm Type
Experimental
Arm Description
Non-myeloablative conditioning
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab
Other Intervention Name(s)
Campath
Intervention Description
Alemtuzumab, Day -7 to -3. Dose: 0.2mg/kg/dose SC once daily x 5 days
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation
Other Intervention Name(s)
TBI
Intervention Description
TBI 300 cGy on Day -2
Intervention Type
Drug
Intervention Name(s)
Sirolimus
Intervention Description
Sirolimus is used for GVHD prophylaxis
Primary Outcome Measure Information:
Title
Incidence of pure red cell aplasia (PRCA)
Description
Clinical definition: reticulocytopenia < 10x109/L (< 1%) lasting more than 60 days after HSCT, or Pathological definition: the absence of erythroid precursors in the marrow in the setting of adequate myeloid, lymphoid and megakaryocytic precursors
Time Frame
6 months from enrollment
Secondary Outcome Measure Information:
Title
RBC chimerism measured by peripheral blood flow cytometry
Description
Peripheral blood for RBC chimerism on flow sorted erythroid precursor cells
Time Frame
12 months
Title
RBC chimerism measured by bone marrow BFU-erythroid forming colonies
Description
Bone marrow will be performed between Day +45 and +60
Time Frame
2 months
Title
Primary graft failure
Description
Measured by donor chimerism from peripheral blood and bone marrow
Time Frame
6 weeks
Title
Secondary graft failure
Description
Measured by donor chimerism in peripheral blood and bone marrow
Time Frame
24 months
Title
Disease recurrence
Description
Measured by peripheral blood Hb S level
Time Frame
24 months
Title
Incidence and severity of acute GVHD
Description
Acute GVHD grade will be accessed using modified CIBMTR criteria
Time Frame
100 days
Title
Incidence and severity of chronic GVHD
Description
Chronic GVHD will be accessed using the NIH consensus criteria
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must be ≥ 12 months and < 19 years of age at the time of study enrollment.
Patients must have sickle cell disease as defined by hemoglobin electropheresis, as follows:
homozygous Hb S disease (HbSS),
sickle-Hb C disease (HbSC),
sickle beta-plus-thalassemia (HbS/β+), or
sickle beta-null-thalassemia (HbS/βo)
Patients must meet standard eligibility criteria to undergo HSCT, including but not limited to one or more of the following:
history of repeated (more than 1) bony (vaso-occlusive) crisis
history of stroke
elevated transcranial Doppler velocity not eligible for hydroxyurea, as per TWiTCH trial (ie. severe vasculopathy)
history of acute chest crisis or splenic sequestration crisis
history of priapism in males
history of osteonecrosis
pulmonary hypertension as documented by tricuspid regurgitation jet velocity (TRV) > 2.5 m/s on echocardiogram
red cell allo-immunization (≥ 2 antibodies) during long term transfusion therapy
Sickle complications should be present despite the use of hydroxyurea, but this is not an absolute requirement, if the treating team considers the patient to be at high risk for further crisis episodes.
Exclusion Criteria:
Patients who are unable to comply with or follow the study protocol.
Patients with known hypersensitivity to sirolimus, its derivatives or to any of its components.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tony Truong, MD, MPH
Phone
403-955-7272
Email
tony.truong@ahs.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Greg Guilcher, MD
Phone
403-955-7272
Facility Information:
Facility Name
Alberta Children's Hospital
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3B 6A8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tony Truong, MD, MPH
Phone
403-955-7272
Email
tony.truong@ahs.ca
First Name & Middle Initial & Last Name & Degree
Greg Guilcher, MD
Phone
403-955-7272
First Name & Middle Initial & Last Name & Degree
Tony Truong, MD, MPH
First Name & Middle Initial & Last Name & Degree
Greg Guilcher, MD
First Name & Middle Initial & Last Name & Degree
Victor Lewis, MD
First Name & Middle Initial & Last Name & Degree
Michael Leaker, MD
First Name & Middle Initial & Last Name & Degree
Aisha Bruce, MD
First Name & Middle Initial & Last Name & Degree
Aru Narendran, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Nonmyeloablative Stem Cell Transplant in Children With Sickle Cell Disease and a Major ABO-Incompatible Matched Sibling Donor
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