Plain English Summary
Background and study aims:
Thalassemia major (or beta-thalassemia) is a genetic disorder in which there are abnormal beta haemoglobin chains in red blood cells. Patients with thalassemia major require lifelong blood transfusions for survival, but these may bring complications including iron overload, failure to thrive, or transfusion-transmitted infections. Hematopoietic stem cells are the stem cells that give rise to other blood cells. Haematopoietic stem cell transplantation (HSCT) is currently the only cure for thalassemia major. Although alternative donors have greatly improved the choice of donors for thalassemia major patients, long-term safety and effectiveness varies between different protocols. The aim of this study is to investigate the outcomes of thalassemia major patients who received HSCT using a newly developed protocol with alternative donors.
Who can participate?
Patients aged 2 to 18 who have been diagnosed with thalassemia major and have indications for haematopoietic stem cell transplantation
What does the study involve?
All participants receive HSCT using a newly developed protocol with alternative donors. The duration of the treatment will be about 1 year but can be longer depending on the condition of the patient. The follow-up time will be at least 2 years after the transplant but the researchers expect to follow the patients as long as possible.
What are the possible benefits and risks of participating?
The recruited patients will be given the information at the time of recruitment.
Where is the study run from?
Shenzhen Children's Hospital (China)
When is the study starting and how long is it expected to run for?
August 2020 to August 2023
Who is funding the study?
1. Shenzhen Key Medical Discipline Construction Fund (China)
2. Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (China)
3. Sanming Project of Medicine in Shenzhen (China)
Who is the main contact?
Dr Uet Yu
cloveringo69@hotmail.com
Study website
Contact information
Type
Scientific
Contact name
Dr Sixi Liu
ORCID ID
Contact details
7019 Yitian Road
Futian
Shenzhen
518038
China
+86 (0)18938690206
tiger647@126.com
Type
Public
Contact name
Dr Uet Yu
ORCID ID
Contact details
7019 Yitian Road
Futian
Shenzhen
518038
China
+86 (0)13622311888
cloveringo69@hotmail.com
Additional identifiers
EudraCT/CTIS number
Nil known
IRAS number
ClinicalTrials.gov number
Nil known
Protocol/serial number
SZCHXYK2020001
Study information
Scientific title
Combined haematopoietic stem cell transplantation with haploidentical graft and cord blood for paediatric patients with thalassemia major: a single centre, prospective study (SZTM2020)
Acronym
SZTM2020
Study hypothesis
This study is to study the outcomes of patients with thalassemia major who received haematopoietic stem cell transplantation using a protocol developed for haploidentical donors. The primary hypothesis is that this protocol will promote stable engraftment of hematopoietic cells, support normal erythropoiesis, prevent severe graft versus host diseases, life-threatening infections, and other severe transplant-related complications, and result in an event-free survival of > 90% of children with thalassemia major.
Ethics approval(s)
Approved 28/01/2021, Shenzhen Children’s Hospital Ethics Committee (Shenzhen Children’s Hospital, 7019 Yitian Road, Futian, Shenzhen, China; +86 (0)755 8300 8379; seyllwyh@163.com), ref: 202000302
Study design
Non-randomised single-centre study
Primary study design
Interventional
Secondary study design
Non randomised study
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not applicable
Condition
Thalassemia major
Intervention
Conditioning chemotherapy:
1. Cyclophosphamide (CY, 50 mg/kg/day x 2 days, day -8 to -7)
2. Busulfan (BU, 2.8-4.4 mg/kg/day x 3 days, day -6 to -4)
*The dose of BU is determined based on risk assessments of thalassemia patients and adjusted according to pharmacokinetic evaluation after the seventh dose of BU.
3. Fludarabine (FLU, 40 mg/m²/day x 5 days, day -6 to -2)
4. Anti-thymoglobulin (ATG, 1 mg/kg/day x 3 days, day -3 to -1 )
5. Thiotepa (TT, 5 mg/kg/dose x 2 doses at 12 h interval, day -3)
Cell transfusions:
D0: Bone marrow (BM) and/or peripheral blood stem cell (PBSC)
D1: Umbilical cord blood (UCB) and/or peripheral blood stem cell (PBSC)
*Cell dose: A total of up to 20 x 10^8/kg mononuclear cells (MNCs) for patients with negative results for donor-specific antigen (DSA) before transplant. A total of up to 25 x 10^8/kg MNCs for patients with positive DSA results before transplant.
Prophylaxis for graft versus host diseases:
1. Cyclophosphamide (CY, 50 mg/kg/day x 2 days, day +3 to +4)
2. Tacrolimus (FK506, 0.04 mg/kg/d, from day +5)
* The dose of FK506 is adjusted according to blood concentration.
3. Mycophenolate mofetil (MMF, 10 mg/kg/day, from day +5)
The duration from conditioning chemotherapy to the end of GVHD prophylaxis will take approximately 1 year but can be longer depending on the condition of the patient. The follow-up time for patients recruited for this trial will be at least 2 years post-transplant but the researchers expect to follow the patients as long as possible.
Intervention type
Mixed
Primary outcome measure
1. Overall survival (OS) using Kaplan-Meier estimator at 2 years
2. Thalassemia-free survival (TFS) using R at 2 years
Secondary outcome measures
1. Engraftment: myeloid engraftment (absolute neutrophils count ≥ 0.5×10^9/L for 3 consecutive days) at day +30
2. Transplant-related mortality: using Kaplan-Meier estimator at 2 years
3. Cumulative incidence of acute graft versus host disease (GVHD): acute GVHD by day +180. The classification of aGVHD is determined using either Glucksberg scoring system or IBMTR scoring system
4. Cumulative incidence of chronic GVHD by 2 years. The classification of cGVHD is determined according to the overall severity chronic GVHD grading system
5. Cumulative incidence of sinusoidal obstruction syndrome (SOS, also known as hepatic veno-occlusive disease, VOD): cumulative incidence of SOS/VOD at day +180
6. Cumulative incidence of infectious complications: cumulative incidence of bacterial, fungal, and viral infections by 2 years
Overall study start date
01/08/2020
Overall study end date
31/08/2023
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age 2 to 18 years
2. Diagnosed with thalassemia major
3. Indication of haematopoietic stem cell transplantation
4. A cardiac ejection fraction of >50%; normal pulmonary function tests and pulmonary examination results; and normal kidney function
Participant type(s)
Patient
Age group
Child
Lower age limit
2 Years
Upper age limit
18 Years
Sex
Both
Target number of participants
200
Participant exclusion criteria
1. Uncontrolled bacterial, viral, or fungal infections before transplant
2. Severe liver and heart overload: liver MR T2* value > 1.4 ms or heart MR T2* value > 10 ms
3. Any other restriction for transplant
Recruitment start date
01/11/2020
Recruitment end date
28/02/2023
Locations
Countries of recruitment
China
Study participating centre
Shenzhen Children's Hospital
7019 Yitian Road
Futian
Shenzhen
518038
China
Sponsor information
Organisation
Shenzhen Children's Hospital
Sponsor details
7019 Yitian Road
Futian
Shenzhen
518038
China
+86 (0)755-83009876
sz83936209@163.com
Sponsor type
Hospital/treatment centre
Website
ROR
Funders
Funder type
Research organisation
Funder name
Shenzhen Key Medical Discipline Construction Fund (SZXK034)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Sanming Project of Medicine in Shenzhen (SZSM201512033)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (SZGSP012)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal.
Intention to publish date
30/08/2024
Individual participant data (IPD) sharing plan
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.
IPD sharing plan summary
Other
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|