A Trial to Assess Haploidentical T-depleted Stem Cell Transplantation in Patients With SCD

NCT04201210 | Recruiting Phase 2 DMC

• 1 other identifier: T-Haplo for SCD
• Study Type: interventional
• Target: 212
• Locations: 2 countries
• Sites: 9

Brief Summary

HSCT is currently the only curative option for SCD but less than 20% of SCD patients have a MD donor available. So far, all curative approaches beyond a MSD HSCT at young age are non-satisfactory. With the lack of a suitable donor for the vast majority of patients, the major question of this trial is, if a haploidentical αß/CD19+ T-cell depleted HSCT can be a valid alternative to a MSD HSCT. The main challenge in non-malignant diseases is to offer a safe and GvHD-free HSCT without rejection.

Conditions

HbS Disease; Hemoglobin S Disease; Sickle Cell Anemia; Sickle Cell Disorders; Sickling Disorder Due to Hemoglobin S; Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Primary efficacy endpoint: Composite Endpoint: Event free survival (EFS).

  Event is defined as incidence of acute GvHD (Grade III - IV), chronic GvHD (moderate/severe), graft failure (GF), or death (from any reason).

  day 0 - day180

Secondary Outcomes (6)

• Overall survival

  up to 2 years after transplantation

• Disease free survival

  up to 2 years after transplantation

• Graft failure

  up to 2 years after transplantation

• Quality of life: EQ-5D

  up to 2 years after transplantation

• Quality of life: PedsQL

  up to 2 years after transplantation

Study Arms (2)

Experimental Arm

EXPERIMENTAL

Patients with no matched sibling donor (MSD; defined as 8/( or 10/10 allelic match) will be stratified into the experimental arm

Other: TCRα/β+ and CD19+ depleted haploidentical stem cell transplantation

Control Arm

ACTIVE COMPARATOR

Patients with a matched sibling donor (MSD; defined as 8/( or 10/10 allelic match) will be stratified into the control arm

Other: Matched sibling donor transplantation

Interventions

TCRα/β+ and CD19+ depleted haploidentical stem cell transplantation OTHER

Haploidentical 5+/10 HSCT from a relative, α/β T-depleted

Experimental Arm

Matched sibling donor transplantation OTHER

10/10 HSCT - matched family donor

Control Arm

Eligibility Criteria

• Age: 2 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 2yrs to 35yrs
• Homozygous hemoglobin S disease or heterozygous hemoglobin SC or S 0/+
• Study specific consent given
• Preexisting severe or moderate SCD related complications:
• Clinically significant neurological event (stroke) or deficit
• Silent crisis, neurocognitive deficit
• Pathological angio-MRI with TOF Sequence
• TCD velocity \>200 cm/s at 2 occasions \>1 month apart
• More than 5 vaso-occlusive crises (VOC) in the past 1 year or more than 20 VOC in a lifetime
• Two or more episodes of acute chest syndrome (ACS) in a lifetime or one episode of ACS in the past 24 months
• Chronic transfusion requirement or more than 8 transfusions or one exchange transfusion in a lifetime
• Transfusion-refractory allo-immunization
• More than five SCD-related hospitalizations in a lifetime
• Beginning pulmonary hypertension
• Osteonecrosis at more than 2 sites

You may not qualify if:

• Karnofsky or Lansky Performance Score \< 70%
• Patients with donor-specific antibodies (DSA) against the potential stem cell donor by either
• Cell-based crossmatched assays (Complement-dependent cytotoxicity; CDC) or
• Flow cytometry crossmatch test or
• Solid-phase immunoassays (SPI) or
• Modified SPI such as C4d and C1q assays Whichever method the participating center is experienced in.
• Patients with major AB0 incompatibility defined according to EBMT Handbook, Edition 2019 Tab 23.1.:
• ABO incompatibility Recipient Donor Major O A O B O AB A AB B AB
• Cardiac function:
• Ejection fraction at rest \<45.0% on echocardiography or
• Shortening fraction of \<27.0% by echocardiogram or radionuclide scan (MUGA)
• Patients with \> grade II hypertension by Common Toxicity Criteria (CTC)
• Renal function:
• Estimated creatinine clearance (for patients \> 12 years) greater than 50.0 mL/minute
• for pediatric patients (\> 1 year to 12 years), GFR estimated by the updated Schwartz formula ≥ 90.0 mL/min/1.73 m2. If \< 90 mL/min/1.73 m2, renal function must be measured by 24-hour creatinine clearance or nuclear GFR and must be \> 70.0 mL/min/1.73 m2 or

Sponsors & Collaborators

• University of Regensburg: lead

Study Sites (9)

St. Anna Kinderspital

Vienna, Austria

NOT YET RECRUITING

University Hospital Aachen, Children's Hospital

Aachen, Germany

NOT YET RECRUITING

Charité University medicine, Clinic for Hematology, Oncology

Berlin, Germany

NOT YET RECRUITING

University Hospital Duesseldorf, Clinic for Pediatric Oncology, - Hemtaology and Clinical Immunology

Düsseldorf, 40225, Germany

NOT YET RECRUITING

University Hospital of Frankfurt, Clinic for Paediatrics and Adolescent Medicine

Frankfurt, Germany

NOT YET RECRUITING

University Hospital Heidelberg, Department of Pediatric Hematology, Oncology and Immunology

Heidelberg, 69120, Germany

RECRUITING

University Hospital Regensburg, Dept. of Ped. Hematology, Oncology and Stem Cell Transplantation

Regensburg, 93053, Germany

RECRUITING

University Children's Hospital Tübingen

Tübingen, 72076, Germany

RECRUITING

University Children's Hospital Würzburg

Würzburg, 97080 Würzburg, Germany

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Selim Corbacioglu, MD

  University Hospital of Regensburg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Selim Corbacioglu, MD

CONTACT

+49 (0)941 944-2101; Haplo.SCD@ukr.de

Katharina Kleinschmidt, MD

CONTACT

+49 (0)941 944-2101; Haplo.SCD@ukr.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the department

Model Details: Patients who fulfill inclusion criteria will be stratified according to donor availability. Patients with a matched sibling donor (MSD; defined as 8/( or 10/10 allelic match) will be stratified into the control arm.

Study Record Dates

• First Submitted: December 2, 2019
• First Posted: December 17, 2019
• Study Start: June 30, 2021
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2030
• Last Updated: May 13, 2024

Record last verified: 2024-05

Locations

DE (8); AU (1)