HbS DiseasePhase 2NCT04201210
A Trial to Assess Haploidentical T-depleted Stem Cell Transplantation in Patients With SCD
A Phase 2 study testing TCRα/β+ and CD19+ depleted haploidentical stem cell transplantation and Matched sibling donor transplantation in people with HbS Disease and Hemoglobin S Disease, run by University of Regensburg at 9 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 35 years
- Conditions the study is for
- HbS Disease, Hemoglobin S Disease, Sickle Cell Anemia
- What is being tested?
- TCRα/β+ and CD19+ depleted haploidentical stem cell transplantation and Matched sibling donor transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 212 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 30 Jun 2021to 31 Mar 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
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- 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
- Beginning SCD Nephropathy
- Recurrent priapism (>2)
Who cannot join
- 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.
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- 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
- Creatinine clearance below threshold defined for stem cell transplantation according to local clinical standard
- Pulmonary function:
- DLCO >50% (adjusted for hemoglobin), and FVC and FEV1≥50%; children unable to perform for PFTs, O2 saturation <92% on room air.
- Liver function:
- Total bilirubin > 2x the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome) and ALT/AST > 2.5x the upper limit of normal.
- Chronic active viral hepatitis
- Women who are pregnant (positive serum or urine βHCG) or breastfeeding. Note: Women of childbearing potential must have a negative serum pregnancy test at study entry.
- Adults of reproductive potential not willing to use an effective method of birth control during study treatment and for at least 12 months thereafter,
- History of uncontrolled autoimmune disease or on active treatment
- Patient unable to comply with the treatment protocol
- Prior autologous or allogeneic hematopoietic stem cell transplant
- Vaccination with a live virus vaccine during the trial
- HIV infection
- Patients with a history of psychiatric illness or a condition which could interfere with their ability to understand the requirements of the study (this includes alcoholism/drug addiction)
- Patients unwilling or unable to comply with the protocol or unable to give informed consent.
- Concurrent severe or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which by assessment of the treating physician could compromise participation in the study
Trial locations and contacts
9 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
9 sites in 2 countries
Germany8 sites, 8 recruiting
- Not yet recruiting
University Hospital Aachen, Children's Hospital
Aachen
Udo Kontny, MD, ukontny@ukaachen.de
- Not yet recruiting
Charité University medicine, Clinic for Hematology, Oncology
Berlin
Giam Lam Vuong, MD, lam.vuong@charite.de
- Not yet recruiting
University Hospital Duesseldorf, Clinic for Pediatric Oncology, - Hemtaology and Clinical Immunology
Düsseldorf, 40225
Roland Meisel, MD, meisel@med.uni-duesseldorf.de
- Not yet recruiting
University Hospital of Frankfurt, Clinic for Paediatrics and Adolescent Medicine
Frankfurt
Peter Bader, MD, peter.bader@kgu.de
- Recruiting
University Hospital Heidelberg, Department of Pediatric Hematology, Oncology and Immunology
Heidelberg, 69120
Johann Greil, MD, johann.greil@med.uni-heidelberg.de
- Recruiting
University Hospital Regensburg, Dept. of Ped. Hematology, Oncology and Stem Cell Transplantation
Regensburg, 93053
Selim Corbacioglu, MD, 0049 944-2101, haplo.scd@ukr.de
Rainer Spachtholz, haplo.scd@ukr.de
- Recruiting
University Children's Hospital Tübingen
Tübingen, 72076
Peter Lang, MD, peter.lang@med.uni-tuebingen.de
- Recruiting
University Children's Hospital Würzburg
Würzburg, 97080 Würzburg
Matthias Wölfl, MD, Woelfl_M@ukw.de
Austria1 site, 1 recruiting
- Not yet recruiting
St. Anna Kinderspital
Vienna
Eva Sorz, +43(1)40470-4380, eva.sorz@ccri.at
About this study
Official title: A Phase II Stratified Trial to Assess Haploidentical T-depleted Stem Cell Transplantation in Patients With Sickle Cell Disease With no Available Sibling Donor
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.
Read the detailed description
Can an α/ß depleted T-Haplo-HSCT with regard to disease free survival, adverse events and safety be considered equivalent to a matched sibling donor transplantation (MSD), in order to offer cure for the majority of patients with sickle cell disease.
The main questions of this trial are:
- Safety of a α/ß T-depleted haploidentical HSCT
- Incidence of acute and chronic GvHD
- Rate of rejection
- Immune reconstitution
- Fertility It is expected that the use of TCRαβ+ and CD19+ depleted haploidentical cell grafts in combination with the less aggressive and well tolerated conditioning regimen needed for patient preparation will be associated with a low risk of grade II-IV aGVHD and no extensive cGvHD, no graft failure and increase speed, spectrum and functionality of immune system reconstitution. This is supposed to reduce the incidence of severe infections leading to lower rates of transplantation related mortality (TRM).
- Conditions
- HbS Disease, Hemoglobin S Disease, Sickle Cell Anemia, Sickle Cell Disorders, Sickling Disorder Due to Hemoglobin S, Sickle Cell Disease
- Being tested
- TCRα/β+ and CD19+ depleted haploidentical stem cell transplantation, Matched sibling donor transplantation
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TCRα/β+ and CD19+ depleted haploidentical stem cell transplantationOther
Haploidentical 5+/10 HSCT from a relative, α/β T-depleted
Matched sibling donor transplantationOther
10/10 HSCT - matched family donor
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: Matched sibling donor transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: day 0 - day180
Secondary outcomes (6)
Overall survival
Overall survival rate (OS) is defined as time from transplantation to death or last follow-up and will be assessed at Day 100 and after 1 year and 2 years.
Measured: up to 2 years after transplantation
Disease free survival
- Disease-free survival (DFS) is defined as the minimum time to recurrence, to death or to the last follow-up, from the time of transplantation and will be assessed at Day 100 and after 1 year and 2 years.
Measured: up to 2 years after transplantation
Graft failure
defined as initial neutrophil engraftment followed by a decline in ANC <500/µl that is unresponsive to growth factor therapy and/or other intervention
Measured: up to 2 years after transplantation
Quality of life: EQ-5D
Adult patients ≥18 years. The European Quality of Life 5 Dimension (EQ-5D) questionnaire has two components: health state description and evaluation.
In the description part, health status is measured in terms of five dimensions (5D); mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Mobility dimension asks about the person's walking ability. Self-care dimension asks about the ability to wash or dress by oneself, and usual activities dimension measures performance in "work, study, housework, family or leisure activities". In pain/discomfort dimension, it asks how much pain or discomfort they have, and in anxiety/depression dimension, it asks how anxious or depressed they are.
Measured: up to 2 years after transplantation
Quality of life: PedsQL
The Pediatric Quality of Life Inventory (PedsQL) is a 23-item generic health status instrument with parent and child forms that assesses five domains of health (physical functioning, emotional functioning, psychosocial functioning, social functioning, and school functioning) in children and adolescents ages 2 to 18.
Measured: up to 2 years after transplantation
Quality of life: FACT-BMT
Functional Assessment of Cancer Therapy-Bone Marrow Transplant (adult patients ≥18 years). FACT-BMT form was designed to measure the QoL in patients undergoing bone marrow transplantation. It combines the FACT-G, an assessment of physical well-being, social/family well-being, emotional well-being and functional well-being, with Bone Marrow Transplantation Sub-scale(BMTS) to measure the QOL of BMT patients.
Measured: up to 2 years after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2019
- Study start30 Jun 2021
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HbS DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 212 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Regensburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Dr. med. Selim Corbacioglu, University of Regensburg
- Investigators
- Selim Corbacioglu, MD, Principal investigator, University Hospital of Regensburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04201210
- Sponsor's protocol ID
- T-Haplo for SCD
- Status last verified
- May 2024
- First submitted
- 2 Dec 2019
- Last updated
- 13 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Stratified Trial to Assess Haploidentical T-depleted Stem Cell Transplantation in Patients With Sickle Cell Disease With no Available Sibling Donor
- ClinicalTrials.gov ID
- NCT04201210
- Acronym / sponsor ID
- T-Haplo for SCD
- Conditions
- HbS Disease, Hemoglobin S Disease, Sickle Cell Anemia, Sickle Cell Disorders, Sickling Disorder Due to Hemoglobin S, Sickle Cell Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 212 participants (estimated)
- Lead sponsor
- University of RegensburgUniversity, hospital or other
- Study start
- 30 Jun 2021 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 17 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Can an α/ß depleted T-Haplo-HSCT with regard to disease free survival, adverse events and safety be considered equivalent to a matched sibling donor transplantation (MSD), in order to offer cure for the majority of patients with sickle cell disease.
The main questions of this trial are:
- Safety of a α/ß T-depleted haploidentical HSCT
- Incidence of acute and chronic GvHD
- Rate of rejection
- Immune reconstitution
- Fertility It is expected that the use of TCRαβ+ and CD19+ depleted haploidentical cell grafts in combination with the less aggressive and well tolerated conditioning regimen needed for patient preparation will be associated with a low risk of grade II-IV aGVHD and no extensive cGvHD, no graft failure and increase speed, spectrum and functionality of immune system reconstitution. This is supposed to reduce the incidence of severe infections leading to lower rates of transplantation related mortality (TRM).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Other: TCRα/β+ and CD19+ depleted haploidentical stem cell transplantationPatients with no matched sibling donor (MSD; defined as 8/( or 10/10 allelic match) will be stratified into the experimental arm |
| Control Arm | Active comparator | Other: Matched sibling donor transplantationPatients with a matched sibling donor (MSD; defined as 8/( or 10/10 allelic match) will be stratified into the control arm |
Who may qualify
- Ages
- 2 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (17 listed)
- 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:
Key exclusion criteria (31 listed)
- Karnofsky or Lansky Performance Score < 70%
- Patients with donor-specific antibodies (DSA) against the potential stem cell donor by either
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TCRα/β+ and CD19+ depleted haploidentical stem cell transplantationHaploidentical 5+/10 HSCT from a relative, α/β T-depleted | Other | Experimental Arm |
| Matched sibling donor transplantation10/10 HSCT - matched family donor | Other | Control Arm |
Primary outcome
Primary efficacy endpoint: Composite Endpoint: Event free survival (EFS).
Time frame: day 0 - day180
Event is defined as incidence of acute GvHD (Grade III - IV), chronic GvHD (moderate/severe), graft failure (GF), or death (from any reason).
6 secondary outcomes
Overall survival
Time frame: up to 2 years after transplantation
Disease free survival
Time frame: up to 2 years after transplantation
Graft failure
Time frame: up to 2 years after transplantation
Quality of life: EQ-5D
Time frame: up to 2 years after transplantation
Quality of life: PedsQL
Time frame: up to 2 years after transplantation
Quality of life: FACT-BMT
Time frame: up to 2 years after transplantation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Selim Corbacioglu, MD principal investigator
University Hospital of Regensburg
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TCRα/β+ and CD19+ depleted haploidentical stem cell transplantation and Matched sibling donor transplantation in people with HbS Disease and Hemoglobin S Disease, run by University of Regensburg at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Selim Corbacioglu, MD (+49 (0)941 944-2101, Haplo.SCD@ukr.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary efficacy endpoint: Composite Endpoint: Event free survival (EFS). (time frame: day 0 - day180). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2024.