Trial Outcomes & Findings for Haploidentical Allogeneic Transplant With Post-transplant Infusion of Regulatory T-cells (NCT NCT01050764)

Last Updated: 2018-06-27

Results Overview

The maximum-tolerated dose (MTD) was to be determined based on the safety and feasibility observed for a pre-determined set of cellular dose level combinations of regulatory T-cells (T-reg) and conventional T-cells (T-con).

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

10 participants

Primary outcome timeframe

30 days after HSCT infusion

Results posted on

2018-06-27

Participant Flow

Participant milestones

Participant milestones
Measure	Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT) Allogeneic, haploidentical hematopoietic stem cell transplant (allo-HSCT) of bone marrow and/or peripheral blood stem cells, followed by infusion of regulatory T-cells (T-reg) plus conventional CD4 and CD8 T-cells (T-con)
Overall Study STARTED	10
Overall Study Received HSCT Graft	8
Overall Study Received Infusion of T-reg Cells	7
Overall Study Received Infusion of T-con Cells	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT) Allogeneic, haploidentical hematopoietic stem cell transplant (allo-HSCT) of bone marrow and/or peripheral blood stem cells, followed by infusion of regulatory T-cells (T-reg) plus conventional CD4 and CD8 T-cells (T-con)
Overall Study Death, before HSCT	1
Overall Study Donor mobilization failure, death	1
Overall Study Death after HSCT, before T-cell infusion	1

Baseline Characteristics

Haploidentical Allogeneic Transplant With Post-transplant Infusion of Regulatory T-cells

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT) n=10 Participants Allogeneic, haploidentical hematopoietic stem cell transplant (allo-HSCT) of bone marrow and/or peripheral blood stem cells, followed by infusion of regulatory T-cells (T-reg) plus conventional CD4 and CD8 T-cells (T-con)
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 30 days after HSCT infusion

Population: Includes all participants that received HSCT

Outcome measures

Outcome measures
Measure	Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT) n=8 Participants Allogeneic, haploidentical hematopoietic stem cell transplant (allo-HSCT) of bone marrow and/or peripheral blood stem cells, followed by infusion of regulatory T-cells (T-reg) plus conventional CD4 and CD8 T-cells (T-con)
Maximum-tolerated Dose (MTD) of Regulatory and Conventional T-cells	NA cells/kg GvHD was within parameters to continue, but the study was terminated due to poor outcomes prior to sufficient accrual to set the MTD, even at the only dose level tested (1x10e5/kg T-reg cells + 1x10e5/kg T-con cells). Primary outcome result is null.

SECONDARY outcome

Timeframe: 1 year

Population: Population of participants that received HSCT and T-reg plus T-con

The primary outcome was incidence of grade 3 or 4 acute graft-vs-host-disease (aGvHD), reported as the number of participants developing grade 3 or 4 aGvHD.

Outcome measures

Outcome measures
Measure	Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT) n=7 Participants Allogeneic, haploidentical hematopoietic stem cell transplant (allo-HSCT) of bone marrow and/or peripheral blood stem cells, followed by infusion of regulatory T-cells (T-reg) plus conventional CD4 and CD8 T-cells (T-con)
Acute Graft-versus-Host-Disease (aGvHD)	1 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Population of participants that received HSCT and T-reg plus T-con

Assessed as subjects remaining alive 12 months after CD34+ cell infusion (ie, excludes death due to any cause)

Outcome measures

Outcome measures
Measure	Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT) n=7 Participants Allogeneic, haploidentical hematopoietic stem cell transplant (allo-HSCT) of bone marrow and/or peripheral blood stem cells, followed by infusion of regulatory T-cells (T-reg) plus conventional CD4 and CD8 T-cells (T-con)
Overall Survival (OS), 1 Year	2 Participants

SECONDARY outcome

Timeframe: 25 months

Population: Population of participants that received HSCT and T-reg plus T-con

Reported as the median overall survival (OS) in months from infusion of the hematopoietic stem cells (HSCT)

Outcome measures

Outcome measures
Measure	Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT) n=7 Participants Allogeneic, haploidentical hematopoietic stem cell transplant (allo-HSCT) of bone marrow and/or peripheral blood stem cells, followed by infusion of regulatory T-cells (T-reg) plus conventional CD4 and CD8 T-cells (T-con)
Median Overall Survival (OS)	3.7 months Standard Deviation 10

SECONDARY outcome

Timeframe: 1 year

Population of participants that received HSCT and T-reg plus T-con, and developed actue, chronic, or any graft vs host disease (GvHD)

Outcome measures

Outcome measures
Measure	Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT) n=7 Participants Allogeneic, haploidentical hematopoietic stem cell transplant (allo-HSCT) of bone marrow and/or peripheral blood stem cells, followed by infusion of regulatory T-cells (T-reg) plus conventional CD4 and CD8 T-cells (T-con)
To Measure the Incidence and Severity of Acute and Chronic GvHD Acute GvHD	1 Participants
To Measure the Incidence and Severity of Acute and Chronic GvHD Chronic GvHD	2 Participants
To Measure the Incidence and Severity of Acute and Chronic GvHD Any GvHD (actue + chronic)	3 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Population of participants that received HSCT and T-reg plus T-con

Serious infections are reported as the number of participants experienced serious infections.

Outcome measures

Outcome measures
Measure	Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT) n=7 Participants Allogeneic, haploidentical hematopoietic stem cell transplant (allo-HSCT) of bone marrow and/or peripheral blood stem cells, followed by infusion of regulatory T-cells (T-reg) plus conventional CD4 and CD8 T-cells (T-con)
Serious Infections	6 Participants

Adverse Events

Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT)

Serious events: 7 serious events

Other events: 7 other events

Deaths: 9 deaths

Serious adverse events

Serious adverse events
Measure	Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT) n=7 participants at risk Allogeneic, haploidentical hematopoietic stem cell transplant (allo-HSCT) of bone marrow and/or peripheral blood stem cells, followed by infusion of regulatory T-cells (T-reg) plus conventional CD4 and CD8 T-cells (T-con)
Immune system disorders Acute graft vs host disease (GvHD)	42.9% 3/7 • Number of events 3 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Renal and urinary disorders Acute renal failure	28.6% 2/7 • Number of events 2 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Infections and infestations Adenoviral infection	57.1% 4/7 • Number of events 4 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome (ARDS)	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Infections and infestations Bacteremia	42.9% 3/7 • Number of events 3 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
General disorders Cardiorespiratory failure	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
General disorders Death	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Respiratory, thoracic and mediastinal disorders Diffuse alveolar hemorrhage	28.6% 2/7 • Number of events 2 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Blood and lymphatic system disorders Hypocellular marrow	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Gastrointestinal disorders Mucositis	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
General disorders Multi-organ failure	28.6% 2/7 • Number of events 2 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Blood and lymphatic system disorders Pancytopenia	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Progressive disease / relapse / recurrence	100.0% 7/7 • Number of events 7 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Respiratory, thoracic and mediastinal disorders Respiratory failure	28.6% 2/7 • Number of events 2 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.

Other adverse events

Other adverse events
Measure	Allogeneic T-Cell Infusion After Stem Cell Transplant (SCT) n=7 participants at risk Allogeneic, haploidentical hematopoietic stem cell transplant (allo-HSCT) of bone marrow and/or peripheral blood stem cells, followed by infusion of regulatory T-cells (T-reg) plus conventional CD4 and CD8 T-cells (T-con)
Immune system disorders Acute graft vs host disease (aGvHD), gut	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Immune system disorders aGvHD, liver	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Immune system disorders aGvHD, skin	42.9% 3/7 • Number of events 3 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Blood and lymphatic system disorders Neutropenic fever	28.6% 2/7 • Number of events 2 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Gastrointestinal disorders Hemorrhagic cystitis	28.6% 2/7 • Number of events 2 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Gastrointestinal disorders Mucositis	28.6% 2/7 • Number of events 2 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
General disorders Edema, lower extremity	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
General disorders Pain, abdominal	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Infections and infestations Infection	100.0% 7/7 • Number of events 15 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Respiratory, thoracic and mediastinal disorders Hypoxia	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Respiratory, thoracic and mediastinal disorders Tachypnea	57.1% 4/7 • Number of events 4 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.
Vascular disorders Hypotension	14.3% 1/7 • Number of events 1 • 5 years Adverse events are only reported for those participants that received the allogeneic T-cell Infusion after the stem cell transplant (SCT). Those that did not receive the SCT, or received only the SCT but the T-cell infusion, are not included except in the all-cause mortality data.

Additional Information

Everett H Meyer, MD, PhD; Assistant Professor of Medicine

Stanford University Medical Center

Phone: 650-725-5816

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place