Trial Outcomes & Findings for TCRαβ+/CD19+ Depleted Allogeneic Hematopoietic Stem Cell Transplantation for Malignant and Non-malignant Disorders (NCT NCT04088760)

Results Overview

Number of patients who experienced infusion reactions including rash, fever, difficulty breathing, and blood pressure abnormalities at the time of infusion of stem cells.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

100 days

Results posted on

2023-09-08

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	15
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Physician Decision	1

Baseline Characteristics

TCRαβ+/CD19+ Depleted Allogeneic Hematopoietic Stem Cell Transplantation for Malignant and Non-malignant Disorders

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TCRαβ+/CD19+ Depleted HSCT n=15 Participants 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.
Age, Categorical <=18 years	12 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	7 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	4 Participants n=5 Participants
Race/Ethnicity, Customized African American	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TCRαβ+/CD19+ Depleted HSCT n=16 infusions 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.
Incidence of Infusion-related Reactions	1 number of infusion reactions

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TCRαβ+/CD19+ Depleted HSCT n=14 Participants 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.
Engraftment and Sustained Donor Chimerism Neutrophil Engraftment	13 Participants
Engraftment and Sustained Donor Chimerism Sustained donor engraftment at 1 year	5 Participants

SECONDARY outcome

Timeframe: 100 days

Population: 14 patients received 15 transplants.

Patients were monitored for symptoms of acute graft versus host disease including rash, diarrhea, and increased bilirubin using the Modified Glucksberg Criteria.

Outcome measures

Outcome measures
Measure	TCRαβ+/CD19+ Depleted HSCT n=14 Participants 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.
Number of Participants With Acute GVHD	5 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Five patients were evaluable for chronic graft versus host disease at 1 year time point.

Patients were monitored for symptoms of chronic graft versus host disease using the NIH Consensus Criteria.

Outcome measures

Outcome measures
Measure	TCRαβ+/CD19+ Depleted HSCT n=5 Participants 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.
Number of Participants With Chronic GVHD	0 Participants

SECONDARY outcome

Timeframe: 1 year

GVHD-free survival was determined based on the presence or not of acute or chronic GVHD at 1 year.

Outcome measures

Outcome measures
Measure	TCRαβ+/CD19+ Depleted HSCT n=11 Participants 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.
GVHD-free Survival	5 Participants

Adverse Events

TCRαβ+/CD19+ Depleted HSCT

Serious events: 2 serious events

Other events: 7 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	TCRαβ+/CD19+ Depleted HSCT n=15 participants at risk 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.
Infections and infestations Sepsis	13.3% 2/15 • Number of events 2 • Adverse Events were collected for the first week of the study. Serious Adverse Events and All-Cause Mortality were collected up to 1 year. Only events that were determined to be attributable to study intervention noted after the first week were recorded and reported.
Cardiac disorders Pericardial effusion	6.7% 1/15 • Number of events 1 • Adverse Events were collected for the first week of the study. Serious Adverse Events and All-Cause Mortality were collected up to 1 year. Only events that were determined to be attributable to study intervention noted after the first week were recorded and reported.

Other adverse events

Other adverse events
Measure	TCRαβ+/CD19+ Depleted HSCT n=15 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.7% 1/15 • Number of events 1 • Adverse Events were collected for the first week of the study. Serious Adverse Events and All-Cause Mortality were collected up to 1 year. Only events that were determined to be attributable to study intervention noted after the first week were recorded and reported.
Metabolism and nutrition disorders Anorexia	33.3% 5/15 • Number of events 5 • Adverse Events were collected for the first week of the study. Serious Adverse Events and All-Cause Mortality were collected up to 1 year. Only events that were determined to be attributable to study intervention noted after the first week were recorded and reported.
General disorders Worsening pain	20.0% 3/15 • Number of events 3 • Adverse Events were collected for the first week of the study. Serious Adverse Events and All-Cause Mortality were collected up to 1 year. Only events that were determined to be attributable to study intervention noted after the first week were recorded and reported.
Investigations Hypokalemia	6.7% 1/15 • Number of events 1 • Adverse Events were collected for the first week of the study. Serious Adverse Events and All-Cause Mortality were collected up to 1 year. Only events that were determined to be attributable to study intervention noted after the first week were recorded and reported.
Vascular disorders Hypertension	6.7% 1/15 • Number of events 1 • Adverse Events were collected for the first week of the study. Serious Adverse Events and All-Cause Mortality were collected up to 1 year. Only events that were determined to be attributable to study intervention noted after the first week were recorded and reported.
Vascular disorders Hypotension	6.7% 1/15 • Number of events 1 • Adverse Events were collected for the first week of the study. Serious Adverse Events and All-Cause Mortality were collected up to 1 year. Only events that were determined to be attributable to study intervention noted after the first week were recorded and reported.
Infections and infestations Bacteremia (strep mitis)	6.7% 1/15 • Number of events 1 • Adverse Events were collected for the first week of the study. Serious Adverse Events and All-Cause Mortality were collected up to 1 year. Only events that were determined to be attributable to study intervention noted after the first week were recorded and reported.

Additional Information

Rebecca Marsh, MD

Cincinnati Children's Hospital Medical Center

Phone: (513) 803-1139

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place