Haplo T-Cell Depleted Transplantation in High-Risk Sickle Cell Disease

Sickle Cell Disease Clinical Trial

— HaploSCD  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01461837
• Other study ID #: NYMC526-4090
• Secondary ID: FD-R-0004090
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 2012
• Est. completion date: December 2025

Study information

• Verified date: March 2024
• Source: New York Medical College
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 21
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 20 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

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

Locations

Country	Name	City	State
United States	Lurie Children's Hospital	Chicago	Illinois
United States	University of California Los Angeles (UCLA)	Los Angeles	California
United States	Medical College of Wisconsin/Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospital and Research Center Oakland	Oakland	California
United States	Washington University/St. Louis Children's Hospital	Saint Louis	Missouri
United States	New York Medical College	Valhalla	New York

Sponsors (9)

Lead Sponsor	Collaborator
New York Medical College	Ann & Robert H Lurie Children's Hospital of Chicago, Medical College of Wisconsin, Miltenyi Biomedicine GmbH, Tufts Medical Center, UCSF Benioff Children's Hospital Oakland, University of California, Los Angeles, University of California, San Francisco, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	neurological/neurocognitive status	Change from baseline in neurological/neurocognitive status	2 years
Secondary	Pulmonary/pulmonary vascular status	Change from baseline of Pulmonary/pulmonary vascular status	2 years
Secondary	Health-related quality of life	Change from baseline of Health-related quality of life (CHRIs-HSCT/CHRIs-General)	4 years

External Links

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