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Nonmyeloablative Stem Cell Transplant in Children With Sickle Cell Disease and a Major ABO-Incompatible Matched Sibling Donor (Sickle-AID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03214354
Recruitment Status : Recruiting
First Posted : July 11, 2017
Last Update Posted : May 27, 2021
Sponsor:
Information provided by (Responsible Party):
Tony H. Truong, University of Calgary

Study Description
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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.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Stem Cell Transplant Complications Red Blood Cell Disorder Pure Red Cell Aplasia Drug: Alemtuzumab Radiation: Total Body Irradiation Drug: Sirolimus Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 5, 2017
Estimated Primary Completion Date : July 2023
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Organ Donation
Drug Information available for: Alemtuzumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Non-myeloablative conditioning
Non-myeloablative conditioning
 Drug: Alemtuzumab
Alemtuzumab, Day -7 to -3. Dose: 0.2mg/kg/dose SC once daily x 5 days
Other Name: Campath

Radiation: Total Body Irradiation
TBI 300 cGy on Day -2
Other Name: TBI

Drug: Sirolimus
Sirolimus is used for GVHD prophylaxis


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of pure red cell aplasia (PRCA) [ Time Frame: 6 months from enrollment ]
    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 :
  1. RBC chimerism measured by peripheral blood flow cytometry [ Time Frame: 12 months ]
    Peripheral blood for RBC chimerism on flow sorted erythroid precursor cells

  2. RBC chimerism measured by bone marrow BFU-erythroid forming colonies [ Time Frame: 2 months ]
    Bone marrow will be performed between Day +45 and +60

  3. Primary graft failure [ Time Frame: 6 weeks ]
    Measured by donor chimerism from peripheral blood and bone marrow

  4. Secondary graft failure [ Time Frame: 24 months ]
    Measured by donor chimerism in peripheral blood and bone marrow

  5. Disease recurrence [ Time Frame: 24 months ]
    Measured by peripheral blood Hb S level

  6. Incidence and severity of acute GVHD [ Time Frame: 100 days ]
    Acute GVHD grade will be accessed using modified CIBMTR criteria

  7. Incidence and severity of chronic GVHD [ Time Frame: 24 months ]
    Chronic GVHD will be accessed using the NIH consensus criteria


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03214354


Contacts
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Contact: Tony Truong, MD, MPH 403-955-7272 tony.truong@ahs.ca
Contact: Greg Guilcher, MD 403-955-7272

Locations
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Canada, Alberta
Alberta Children's Hospital Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Tony Truong, MD, MPH    403-955-7272    tony.truong@ahs.ca   
Contact: Greg Guilcher, MD    403-955-7272      
Principal Investigator: Tony Truong, MD, MPH         
Sub-Investigator: Greg Guilcher, MD         
Sub-Investigator: Victor Lewis, MD         
Sub-Investigator: Michael Leaker, MD         
Sub-Investigator: Aisha Bruce, MD         
Sub-Investigator: Aru Narendran, MD, PhD         
Sponsors and Collaborators
University of Calgary
More Information
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Responsible Party: Tony H. Truong, Pediatric Hematologist/Oncologist, University of Calgary
ClinicalTrials.gov Identifier: NCT03214354    
Other Study ID Numbers: TRU-17-001
First Posted: July 11, 2017    Key Record Dates
Last Update Posted: May 27, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Tony H. Truong, University of Calgary:
sickle cell disease
stem cell transplant
red blood cell engraftment
nonmyeloablative
pure red cell aplasia
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Red-Cell Aplasia, Pure
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Sirolimus
Alemtuzumab
 Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological