Haplo T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease (HaploSCD)

Familial Haploidentical T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease (IND 14359)

This study is being done to determine the safety and outcome (long-term control) of a high-dose chemotherapy regimen followed by an infusion of CD34 selected (immune cells) stem cells from a partially matched adult family member donor, called haploidentical stem cell transplantation, in high-risk sickle cell disease patients.

Funding Source - FDA OOPD

Study Overview

• Status: Active, not recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: CD34 selected T-cell depleted allogeneic SCT

Detailed Description

The purpose of this study is to investigate host myeloimmunosuppressive conditioning followed by familial haploidentical T cell depleted allogeneic stem cell transplantation in patients with high risk Sickle Cell Disease (SCD). It is hypothesized that it will be safe and well tolerated, and result in sustained donor chimerism, acceptable engraftment and immune reconstitution. Also, that it will limit SCD related organ damage resulting in improved and/or stable neurological, neurocognitive, pulmonary and pulmonary vascular function and health related quality of life (QOL).

Patients 2-20.99 years of age with a diagnosis of high-risk SCD and with an unaffected HLA partially matched family donor and meeting eligibility criteria (inclusion and exclusion criteria) are eligible.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles (UCLA)
    • Oakland, California, United States, 94609
      • Children's Hospital and Research Center Oakland
  • Illinois
    • Chicago, Illinois, United States, 60611-2605
      • Lurie Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University/St. Louis Children's Hospital
  • New York
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin/Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Homozygous Hemoglobin S Disease, or Hemoglobin S Beta0/+ thalassemia

• Patients must demonstrate one or more of the following Sickle Cell Disease Complications

  1. Clinically significant neurologic event (stroke) or any neurologic deficit lasting >24 hours that is accompanied by an infarct on cerebral MRI
  2. Minimum of two episodes of acute chest syndrome.
  3. Recurrent painful events (at least 3 in the 2 years prior to enrollment).
  4. Abnormal TCD study requiring starting on chronic transfusion therapy.
  5. At least one silent infarct lesion on a MRI scan of the head.
• A familial haploidentical donor without homozygous sickle cell disease
• Adequate organ function (renal, liver, cardiac and pulmonary function)
• Karnofsky or Lansky (age appropriate) Performance Score ≥50%
• Liver biopsy is optional to assess for iron overload in chronically transfused patients.

Exclusion Criteria:

• Females who are pregnant or breast-feeding
• SCD Patients with documented uncontrolled infection
• SCD patients who have an unaffected HLA matched family donor willing to proceed to donation
• Karnofsky/Lansky (age appropriate) Performance Score <50% (hemiplegia alone secondary to a previous stroke is not an exclusion)
• Demonstrated lack of compliance with medical care.
• Clinically significant fibrosis or cirrhosis of the liver
• Previously received a HSCT

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Haplo Stem Cell Transplantation; CD34 selected T-cell depleted allogeneic SCT

Drug: CD34 selected T-cell depleted allogeneic SCT; Hydroxyurea (60 mg/kg/day) and azathioprine (3 mg/kg/day) day -59 to day -11; fludarabine (30 mg/m2) Days -17, -16, -15, -14, -13; busulfan (3.2 mg/kg/day) Days -12, -11, -10, -9; thiotepa (10 mg/kg IV) day -8; cyclophosphamide (50 mg/kg) Days -7, -6, -5, -4; TLI on day -3; rabbit ATG (2.0 mg/kg/day) day -5,-4,-3, and -2; Stem Cell infusion day 0; Other Names: allogeneic stem cell transplantation; Familial haploidentical; T-cell depleted; high risk Sickle Cell Disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment related events	Death, primary or late graft rejection, or recurrence of disease and acceptable rate of hematopoietic engraftment, acute and chronic graft-versus-host disease	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
neurological/neurocognitive status	Change from baseline in neurological/neurocognitive status	2 years
Pulmonary/pulmonary vascular status	Change from baseline of Pulmonary/pulmonary vascular status	2 years
Health-related quality of life	Change from baseline of Health-related quality of life (CHRIs-HSCT/CHRIs-General)	4 years

Collaborators and Investigators

• Sponsor: New York Medical College
• Collaborators: Washington University School of Medicine; University of California, Los Angeles; Medical College of Wisconsin; University of California, San Francisco; Ann & Robert H Lurie Children's Hospital of Chicago; Tufts Medical Center; Miltenyi Biomedicine GmbH; UCSF Benioff Children's Hospital Oakland
• Investigators: Principal Investigator: Mitchell S Cairo, MD, New York Medical College

Publications and helpful links

General Publications

• Parsons SK, Rodday AM, Weidner RA, Morris E, Braniecki S, Shenoy S, Talano JA, Moore TB, Panarella A, Flower A, Milner J, Fabricatore S, Mahanti H, van de Ven C, Shi Q, Cairo MS. Significant improvement of child physical and emotional functioning after familial haploidentical stem cell transplant. Bone Marrow Transplant. 2022 Apr;57(4):586-592. doi: 10.1038/s41409-022-01584-y. Epub 2022 Feb 2.

Helpful Links

• Consortium website for Parent-to-Child (haplo) Bone Marrow Transplant for Sickle Cell Disease (SCD)

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: October 19, 2011
• First Submitted That Met QC Criteria: October 26, 2011
• First Posted (Estimated): October 28, 2011

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: stem cell transplantation; sickle cell disease; haploidentical
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: NYMC526-4090; FD-R-0004090 (Other Grant/Funding Number: FDA OOPD)