A Trial to Assess Haploidentical T-depleted Stem Cell Transplantation in Patients With SCD
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04201210|
Recruitment Status : Not yet recruiting
First Posted : December 17, 2019
Last Update Posted : April 9, 2021
|Condition or disease||Intervention/treatment||Phase|
|HbS Disease Hemoglobin S Disease Sickle Cell Anemia Sickle Cell Disorders Sickling Disorder Due to Hemoglobin S Sickle Cell Disease||Other: TCRα/β+ and CD19+ depleted haploidentical stem cell transplantation Other: Matched sibling donor transplantation||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||212 participants|
|Intervention Model:||Parallel Assignment|
|Intervention 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)|
|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|
|Estimated Study Start Date :||June 1, 2021|
|Estimated Primary Completion Date :||March 31, 2026|
|Estimated Study Completion Date :||March 31, 2027|
Experimental: Experimental Arm
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
Haploidentical 5+/10 HSCT from a relative, α/β T-depleted
Active Comparator: Control Arm
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
10/10 HSCT - matched family donor
- 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).
- Overall survival [ Time Frame: up to 2 years after transplantation ]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.
- Disease free survival [ Time Frame: up to 2 years after transplantation ]• 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.
- Graft failure [ Time Frame: up to 2 years after transplantation ]defined as initial neutrophil engraftment followed by a decline in ANC <500/µl that is unresponsive to growth factor therapy and/or other intervention
- Quality of life: EQ-5D [ Time Frame: up to 2 years after transplantation ]
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.
- Quality of life: PedsQL [ Time Frame: up to 2 years after transplantation ]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.
- Quality of life: FACT-BMT [ Time Frame: up to 2 years after transplantation ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04201210
|Contact: Selim Corbacioglu, MD||+49 (0)941 944-2101||Haplo.SCD@ukr.de|
|Contact: Katharina Kleinschmidt, MD||+49 (0)941 944-2101||Haplo.SCD@ukr.de|
|Principal Investigator:||Selim Corbacioglu, MD||University Hospital of Regensburg|