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

• ClinicalTrials.gov Identifier: NCT03214354
• Recruitment Status: Recruiting
• First Posted: July 11, 2017
• Last Update Posted: May 27, 2021
• Sponsor: University of Calgary
• Information provided by (Responsible Party): Tony H. Truong, University of Calgary

Tracking Information

• First Submitted Date: July 5, 2017
• First Posted Date: July 11, 2017
• Last Update Posted Date: May 27, 2021
• Actual Study Start Date: July 5, 2017
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 10, 2017)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 10, 2017)

• RBC chimerism measured by peripheral blood flow cytometry [ Time Frame: 12 months ]
  Peripheral blood for RBC chimerism on flow sorted erythroid precursor cells
• RBC chimerism measured by bone marrow BFU-erythroid forming colonies [ Time Frame: 2 months ]
  Bone marrow will be performed between Day +45 and +60
• Primary graft failure [ Time Frame: 6 weeks ]
  Measured by donor chimerism from peripheral blood and bone marrow
• Secondary graft failure [ Time Frame: 24 months ]
  Measured by donor chimerism in peripheral blood and bone marrow
• Disease recurrence [ Time Frame: 24 months ]
  Measured by peripheral blood Hb S level
• Incidence and severity of acute GVHD [ Time Frame: 100 days ]
  Acute GVHD grade will be accessed using modified CIBMTR criteria
• Incidence and severity of chronic GVHD [ Time Frame: 24 months ]
  Chronic GVHD will be accessed using the NIH consensus criteria

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Nonmyeloablative Stem Cell Transplant in Children With Sickle Cell Disease and a Major ABO-Incompatible Matched Sibling Donor
• 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

Condition

• Sickle Cell Disease
• Stem Cell Transplant Complications
• Red Blood Cell Disorder
• Pure Red Cell Aplasia

Intervention

• 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

Study Arms

Experimental: Non-myeloablative conditioning

Non-myeloablative conditioning

Interventions:

• Drug: Alemtuzumab
• Radiation: Total Body Irradiation
• Drug: Sirolimus

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 10, 2017): 12
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2024
• Estimated Primary Completion Date: July 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 19 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

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

Contact: Greg Guilcher, MD; 403-955-7272

• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT03214354
• Other Study ID Numbers: TRU-17-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Tony H. Truong, University of Calgary
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Calgary
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University of Calgary
• Verification Date: May 2021