Trial Outcomes & Findings for Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts in Preventing GVHD in Children (NCT NCT01858740)
NCT ID: NCT01858740
Last Updated: 2024-03-12
Results Overview
Graft failure defined as failure to reach ANC of \>500/uL for 3 consecutive days by day 28, or irreversible decrease in ANC to \<100 after an established donor graft. A reduction in ANC as result of relapse is not considered graft failure
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Up to 5 years
Results posted on
2024-03-12
Participant Flow
Participants were recruited based on referral for Hematopoietic Cell transplant at Fred Hutchinson Cancer Center between March 2014 and January 2017. The first participant was enrolled on April 10, 2014 and the last participant was enrolled on January 27, 2017.
Of the 20 patients enrolled, all 20 met inclusion criteria and went forward to be treated on the study.
Participant milestones
| Measure |
Treatment (CD45RA+ T Cell Depleted PBSCT)
CONDITIONING REGIMEN: Patients undergo TBI BID on days -10 to -7, receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
TRANSPLANT: Patients undergo CD34+ enriched, CD45RA+ T cell-depleted allogeneic PBSCT on day 0.
POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV continuously or PO every 12 hours beginning on day -1 and continuing through day 50 with taper. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Allogeneic Hematopoietic Stem Cell Transplantation: Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Fludarabine Phosphate: Given IV
Laboratory Biomarker Analysis: Correlative studies
Methotrexate: Given IV
Peripheral Blood Stem Cell Transplantation: Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
T Cell-Depleted Hematopoietic Stem Cell Transplantation: Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Tacrolimus: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo TBI
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
Day 28 Post Transplant
|
20
|
|
Overall Study
Day 100 Post Transplant
|
18
|
|
Overall Study
1 Year Post Transplant
|
18
|
|
Overall Study
COMPLETED
|
16
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Treatment (CD45RA+ T Cell Depleted PBSCT)
CONDITIONING REGIMEN: Patients undergo TBI BID on days -10 to -7, receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
TRANSPLANT: Patients undergo CD34+ enriched, CD45RA+ T cell-depleted allogeneic PBSCT on day 0.
POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV continuously or PO every 12 hours beginning on day -1 and continuing through day 50 with taper. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Allogeneic Hematopoietic Stem Cell Transplantation: Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Fludarabine Phosphate: Given IV
Laboratory Biomarker Analysis: Correlative studies
Methotrexate: Given IV
Peripheral Blood Stem Cell Transplantation: Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
T Cell-Depleted Hematopoietic Stem Cell Transplantation: Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Tacrolimus: Given IV or PO
Thiotepa: Given IV
Total-Body Irradiation: Undergo TBI
|
|---|---|
|
Overall Study
Death
|
4
|
Baseline Characteristics
Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts in Preventing GVHD in Children
Baseline characteristics by cohort
| Measure |
Overall Study Participants
n=20 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis (Day -1 to Day 50, then tapered from day 50)
|
|---|---|
|
Age, Categorical
<=18 years
|
20 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 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
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
19 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 5 yearsGraft failure defined as failure to reach ANC of \>500/uL for 3 consecutive days by day 28, or irreversible decrease in ANC to \<100 after an established donor graft. A reduction in ANC as result of relapse is not considered graft failure
Outcome measures
| Measure |
Overall Study Participants
n=20 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Graft Failure
Fail to engraft by D28
|
0 Participants
|
|
Graft Failure
Fail to maintain ANC >100 for 5 years
|
1 Participants
|
PRIMARY outcome
Timeframe: 5 years post transplantMeasure the number of days to discontinuation of systemic immunosuppression (both including and excluding calcineurin inhibitors) in pediatric recipients of CD45RA+ T cell-depleted PBSCT. Possible outcomes range from no systemic immunosuppression (best outcome) to 5 years on immunosuppression (poor outcome)
Outcome measures
| Measure |
Overall Study Participants
n=18 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Time to Discontinuation of Systemic Immunosuppression
Discontinuation (or never started) prednisone
|
106 Days
Interval 87.0 to 238.0
|
|
Time to Discontinuation of Systemic Immunosuppression
Discontinuation of systemic immunosuppression (including calcineurin inhibitors)
|
349 Days
Interval 266.0 to 405.0
|
SECONDARY outcome
Timeframe: Up to 5 yearsNumber of days post-transplant without transfusion where platelet count is \>50,000/uL. Measured as the first of three days
Outcome measures
| Measure |
Overall Study Participants
n=20 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Time to Platelet Count > 50,000/uL for 3 Days Without Transfusion
|
23 Days
Interval 21.0 to 29.0
|
SECONDARY outcome
Timeframe: Up to 5 yearsNumber of days post transplant until platelet count is \>20,000/uL for three consecutive days without transfusion, counted as the first of three days
Outcome measures
| Measure |
Overall Study Participants
n=20 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Time to Platelet Count > 20,000/uL for 3 Days Without Transfusion
|
19.5 Days
Interval 16.0 to 26.0
|
SECONDARY outcome
Timeframe: Up to 5 yearsTime (in days) to ANC of \> 1,000/uL, counted as the first of three consecutive days post-transplant
Outcome measures
| Measure |
Overall Study Participants
n=20 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Time to ANC of > 1,000/uL
|
23 Days
Interval 19.75 to 28.0
|
SECONDARY outcome
Timeframe: Up to 5 yearsTime (in days) to ANC of \> 500/uL, counted as the first of three consecutive days post-transplant
Outcome measures
| Measure |
Overall Study Participants
n=20 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Time to ANC of > 500/uL
|
20.5 Days
Interval 19.0 to 24.0
|
SECONDARY outcome
Timeframe: Up to 5 yearsNumber of patients with chronic GVHD defined using NIH criteria. Incidents requiring only calcineurin inhibitors will not be counted. If patients do not develop cGVHD after transplant but then relapse and then receive a donor lymphocyte infusion or antigen specific T cells as treatment, they will no longer be evaluable for the cGVHD endpoint.
Outcome measures
| Measure |
Overall Study Participants
n=18 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Occurrence of Chronic GHVD Meeting NIH Criteria and Requiring Systemic Pharmacological Immunosuppression
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to day 100Number of patients with acute GVHD grade III-IV
Outcome measures
| Measure |
Overall Study Participants
n=20 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Acute GVHD Grade III-IV
Grade III acute GVHD
|
2 Participants
|
|
Acute GVHD Grade III-IV
Grade IV acute GVHD
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to day 100Number of patients with acute GVHD grades II-IV
Outcome measures
| Measure |
Overall Study Participants
n=20 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Acute GVHD Grades II-IV
Grade II acute GVHD
|
15 Participants
|
|
Acute GVHD Grades II-IV
Grade III acute GVHD
|
2 Participants
|
|
Acute GVHD Grades II-IV
Grade IV acute GVHD
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to day 100Presence of steroid refractory acute GVHD within the first 100 days post transplant
Outcome measures
| Measure |
Overall Study Participants
n=18 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Steroid Refractory Acute GVHD
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 5 yearsRelapse defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology
Outcome measures
| Measure |
Overall Study Participants
n=20 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Relapse Post-transplant
Relapse in first 100 days
|
0 Participants
|
|
Relapse Post-transplant
Relapse between day 101 to 6 months
|
0 Participants
|
|
Relapse Post-transplant
Relapse between 6 months to 1 year
|
2 Participants
|
|
Relapse Post-transplant
Relapse between 1 to 5 years
|
1 Participants
|
|
Relapse Post-transplant
Total relapse in first 5 years
|
3 Participants
|
SECONDARY outcome
Timeframe: Up to 5 yearsTransplant related mortality defined as mortality in any patient for whom there has not been a diagnosis of relapse
Outcome measures
| Measure |
Overall Study Participants
n=20 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Transplant Related Mortality
|
3 Participants
|
SECONDARY outcome
Timeframe: Up to 5 yearsUse of additional immune suppressive agents to treat chronic GVHD other than first line therapy. First line therapy is considered prednisone and tacrolimus/cyclosporin.
Outcome measures
| Measure |
Overall Study Participants
n=18 Participants
All participants in single arm study received CD45RA+ T cell depletion PBSC transplant and IV Methotrexate and tacrolimus for GVHD prophylaxis
|
|---|---|
|
Use of Additional Immune Suppressive Agents to Treat Chronic GVHD
|
0 Immunosuppressive agents
|
Adverse Events
Treatment (CD45RA+ T Cell Depleted PBSCT)
Serious events: 0 serious events
Other events: 20 other events
Deaths: 4 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment (CD45RA+ T Cell Depleted PBSCT)
n=20 participants at risk
Single arm study: CD45RA+ T cell depletion PBSC transplant and Methotrexate and tacrolimus for GVHD prophylaxis (Day -1 to Day 50, then tapered from day 50)
|
|---|---|
|
Blood and lymphatic system disorders
Hemolytic uremic syndrome
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Cardiac disorders
Pericardial effusion
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Cardiac disorders
Sinus tachycardia
|
10.0%
2/20 • Number of events 2 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Gastrointestinal disorders
Abdominal pain
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Gastrointestinal disorders
Diarrhea
|
40.0%
8/20 • Number of events 12 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Gastrointestinal disorders
Ileus
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Gastrointestinal disorders
Mucositis oral
|
95.0%
19/20 • Number of events 19 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Gastrointestinal disorders
Nausea
|
65.0%
13/20 • Number of events 15 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Gastrointestinal disorders
Vomiting
|
15.0%
3/20 • Number of events 3 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
General disorders
Multi-organ failure
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Hepatobiliary disorders
SOS/VOD
|
20.0%
4/20 • Number of events 4 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
Enterocolitis infectious
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
C. difficile
|
15.0%
3/20 • Number of events 4 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
CMV reactivation
|
30.0%
6/20 • Number of events 7 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
Blood stream infections not including sepsis
|
40.0%
8/20 • Number of events 10 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
Sepsis
|
10.0%
2/20 • Number of events 2 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
Lung Infection
|
15.0%
3/20 • Number of events 3 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
Skin infection
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
Upper respiratory infection
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
Urinary tract infection
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Investigations
Alanine aminotransferase increased
|
35.0%
7/20 • Number of events 10 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Investigations
Aspartate aminotransferase increased
|
10.0%
2/20 • Number of events 2 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Investigations
CD4 lymphocytes decreased
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Investigations
Creatinine increased
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Investigations
Lymphocyte count decreased
|
60.0%
12/20 • Number of events 12 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Investigations
Neutrophil count decreased
|
25.0%
5/20 • Number of events 5 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Investigations
Platelet count decreased
|
40.0%
8/20 • Number of events 8 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Investigations
White blood cell decreased
|
25.0%
5/20 • Number of events 5 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Metabolism and nutrition disorders
Anorexia
|
50.0%
10/20 • Number of events 11 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
25.0%
5/20 • Number of events 6 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
5.0%
1/20 • Number of events 2 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Metabolism and nutrition disorders
Hypokalemia
|
10.0%
2/20 • Number of events 3 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Metabolism and nutrition disorders
Hyponatremia
|
10.0%
2/20 • Number of events 2 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Nervous system disorders
Headache
|
10.0%
2/20 • Number of events 2 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Nervous system disorders
Tremor
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Renal and urinary disorders
Acute kidney injury
|
15.0%
3/20 • Number of events 3 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Renal and urinary disorders
Hematuria
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
10.0%
2/20 • Number of events 2 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
15.0%
3/20 • Number of events 3 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
5.0%
1/20 • Number of events 1 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
15.0%
3/20 • Number of events 3 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Vascular disorders
Hypertension
|
25.0%
5/20 • Number of events 8 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
Catheter related infection
|
10.0%
2/20 • Number of events 2 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
Mucosal infection
|
15.0%
3/20 • Number of events 3 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
|
Infections and infestations
Abdominal Infection
|
10.0%
2/20 • Number of events 2 • AEs and SAEs: Conditioning through D100; All cause mortality: Conditioning through 5 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place