Allogeneic Hematopoietic Cell Transplantation
Conditions
Brief summary
The purpose of this study is to investigate the safety and efficacy of TCRαβ+/CD19+ depleted allogeneic hematopoietic stem cell transplant (HSCT) for malignant and non-malignant disorders in children and adolescent/young adult patients using the CliniMACS® immunomagnetic selection device (Miltenyi Biotec).
Detailed description
Acute graft versus host disease (GVHD) remains a significant cause of morbidity and mortality and is the biggest barrier to successful allogeneic hematopoietic cell transplantation (HSCT) outcomes. Improved methods of acute GVHD prevention are needed. TCRαβ+/CD19+ depletion of allogeneic hematopoietic stem cell products offers an opportunity to limit the risk of acute GVHD by removing TCRαβ+ T cells and CD19+ B cells which participate in acute GVHD initiation and perpetuation. The purpose of this study is to investigate the safety and efficacy of TCRαβ+/CD19+ depleted allogeneic hematopoietic stem cell transplant (HSCT) for malignant and non-malignant disorders in children and adolescent/young adult patients using the CliniMACS® immunomagnetic selection device (Miltenyi Biotec).
Interventions
DRUGTCRαβ+/CD19+ depleted allogeneic hematopoietic stem cell transplant (HSCT)
The majority of TCRαβ+ T cells and CD19+ B cells will be removed from the allogeneic graft utilizing the CliniMACS® immunomagnetic selection device (Miltenyi Biotec). The depletion process involves two phases; cell labeling (phase 1) and the automated immunomagnetic depletion process (phase 2). The CD34+ dose may be adjusted by the need to not exceed the TCRαβ+CD3+ dose threshold.
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Any patient being treated at Cincinnati Children's Hospital requiring an allogeneic HSCT who lacks an HLA-genotypically matched related donor. Genotypically matched related donors are allowed when there is a clinical desire to avoid the use of GVHD prophylaxis medications.
Exclusion criteria
* Prior allogeneic transplant with active acute or chronic GVHD, or life-threatening infection. Patients with a prior history of allogenic transplant without active GVHD or life-threatening infection can be considered.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Infusion-related Reactions | 100 days | Number of patients who experienced infusion reactions including rash, fever, difficulty breathing, and blood pressure abnormalities at the time of infusion of stem cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Engraftment and Sustained Donor Chimerism | 28 days and 1 year | Initial neutrophil engraftment prior to day +28 was determined by monitoring for neutrophil count recovery post-transplant and performing blood tests to confirm presence of donor cells. Sustained donor chimerism at 1 year post transplant was determined again by performing blood tests to confirm presence of donor cells. |
| Number of Participants With Acute GVHD | 100 days | Patients were monitored for symptoms of acute graft versus host disease including rash, diarrhea, and increased bilirubin using the Modified Glucksberg Criteria. |
| Number of Participants With Chronic GVHD | 1 year | Patients were monitored for symptoms of chronic graft versus host disease using the NIH Consensus Criteria. |
| GVHD-free Survival | 1 year | GVHD-free survival was determined based on the presence or not of acute or chronic GVHD at 1 year. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TCRαβ+/CD19+ Depleted HSCT TCRαβ+/CD19+ depleted allogeneic hematopoietic stem cell transplant (HSCT): The majority of TCRαβ+ T cells and CD19+ B cells will be removed from the allogeneic graft utilizing the CliniMACS® immunomagnetic selection device (Miltenyi Biotec). The depletion process involves two phases; cell labeling (phase 1) and the automated immunomagnetic depletion process (phase 2). The CD34+ dose may be adjusted by the need to not exceed the TCRαβ+CD3+ dose threshold. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | TCRαβ+/CD19+ Depleted HSCT |
|---|---|
| Age, Categorical <=18 years | 12 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Race/Ethnicity, Customized African American | 2 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 7 Participants |
| Race/Ethnicity, Customized Hispanic | 4 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 15 |
| other Total, other adverse events | 7 / 15 |
| serious Total, serious adverse events | 2 / 15 |
Outcome results
Primary
Incidence of Infusion-related Reactions
Number of patients who experienced infusion reactions including rash, fever, difficulty breathing, and blood pressure abnormalities at the time of infusion of stem cells.
Time frame: 100 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TCRαβ+/CD19+ Depleted HSCT | Incidence of Infusion-related Reactions | 1 number of infusion reactions |
Secondary
Engraftment and Sustained Donor Chimerism
Initial neutrophil engraftment prior to day +28 was determined by monitoring for neutrophil count recovery post-transplant and performing blood tests to confirm presence of donor cells. Sustained donor chimerism at 1 year post transplant was determined again by performing blood tests to confirm presence of donor cells.
Time frame: 28 days and 1 year
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TCRαβ+/CD19+ Depleted HSCT | Engraftment and Sustained Donor Chimerism | Neutrophil Engraftment | 13 Participants |
| TCRαβ+/CD19+ Depleted HSCT | Engraftment and Sustained Donor Chimerism | Sustained donor engraftment at 1 year | 5 Participants |
Secondary
GVHD-free Survival
GVHD-free survival was determined based on the presence or not of acute or chronic GVHD at 1 year.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TCRαβ+/CD19+ Depleted HSCT | GVHD-free Survival | 5 Participants |
Secondary
Number of Participants With Acute GVHD
Patients were monitored for symptoms of acute graft versus host disease including rash, diarrhea, and increased bilirubin using the Modified Glucksberg Criteria.
Time frame: 100 days
Population: 14 patients received 15 transplants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TCRαβ+/CD19+ Depleted HSCT | Number of Participants With Acute GVHD | 5 Participants |
Secondary
Number of Participants With Chronic GVHD
Patients were monitored for symptoms of chronic graft versus host disease using the NIH Consensus Criteria.
Time frame: 1 year
Population: Five patients were evaluable for chronic graft versus host disease at 1 year time point.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TCRαβ+/CD19+ Depleted HSCT | Number of Participants With Chronic GVHD | 0 Participants |