Trial Outcomes & Findings for T-cell Depleted Alternative Donor Transplantation (NCT NCT00968864)

NCT ID: NCT00968864

Last Updated: 2022-04-22

Results Overview

Severe GVHD defined as grade III/IV GVHD.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 53 participants
• Primary outcome timeframe: Within 30 days after stem cell transplant
• Results posted on: 2022-04-22

Participant Flow

Candidates for bone marrow transplant who did not have a healthy HLA-identical related donor, at Levine Children's Hospital between December 2009 and June 2016.

Subjects were enrolled to two cohorts based on donor type, Mismatched Related Donor (MMRD) and Matched Unrelated Donor (MUD).

Participant milestones

Measure	T Cell Depletion Using CliniMACS® Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.
Overall Study STARTED	53
Overall Study COMPLETED	52
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

T Cell Depletion Using CliniMACS® Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.

Overall Study Protocol exception/ not evaluable

1

Baseline Characteristics

T-cell Depleted Alternative Donor Transplantation

Baseline characteristics by cohort

Measure	T Cell Depletion Using CliniMACS® n=52 Participants Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.
Age, Customized Less than 1 year	4 Participants n=5 Participants
Age, Customized 1-2 years	3 Participants n=5 Participants
Age, Customized 2-4 years	5 Participants n=5 Participants
Age, Customized 4-6 years	6 Participants n=5 Participants
Age, Customized 6-8 years	3 Participants n=5 Participants
Age, Customized 8-10 years	4 Participants n=5 Participants
Age, Customized 10-12 years	6 Participants n=5 Participants
Age, Customized 12-14 years	5 Participants n=5 Participants
Age, Customized 14-16 years	5 Participants n=5 Participants
Age, Customized 16-18 years	8 Participants n=5 Participants
Age, Customized Greater than 18 years	3 Participants n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	10 Participants n=5 Participants
Race/Ethnicity, Customized African American	26 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	13 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 30 days after stem cell transplant

Severe GVHD defined as grade III/IV GVHD.

Outcome measures

Measure	T Cell Depletion Using CliniMACS® n=52 Participants Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.	Matched Unrelated Donor Cohort	Matched Unrelated Donor Cohort Number of recipients alive following bone marrow transplant for non-malignant disease.
Number of Participants With Severe Graft vs. Host Disease (GVHD).	0 Participants	—	—

SECONDARY outcome

Timeframe: Within 28 days after stem cell transplant

Population: There were 2 cases of primary graft failure in the mismatched related donor cohort; both achieved engraftment following a second transplant.

Engraftment was measured as time to absolute neutrophil count >500

Outcome measures

Measure	T Cell Depletion Using CliniMACS® n=41 Participants Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.	Matched Unrelated Donor Cohort n=9 Participants	Matched Unrelated Donor Cohort Number of recipients alive following bone marrow transplant for non-malignant disease.
Number of Participants With Engraftment and Time to Engraftment	15 days Interval 9.0 to 19.0	13 days Interval 10.0 to 15.0	—

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Measure	T Cell Depletion Using CliniMACS® n=52 Participants Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.	Matched Unrelated Donor Cohort	Matched Unrelated Donor Cohort Number of recipients alive following bone marrow transplant for non-malignant disease.
Number of Participants With Post-transplant Infections Nocardia	2 Participants	—	—
Number of Participants With Post-transplant Infections Septic arthritis (prosthetic joint)	1 Participants	—	—
Number of Participants With Post-transplant Infections HHV-6 reactivation, no disease	39 Participants	—	—
Number of Participants With Post-transplant Infections Viral URI (adeno, paraflu, rhino, rsv)	25 Participants	—	—
Number of Participants With Post-transplant Infections Clostridium difficile colitis	24 Participants	—	—
Number of Participants With Post-transplant Infections Adenovirus reactivation, no disease	15 Participants	—	—
Number of Participants With Post-transplant Infections Bacteremia, gram positive	12 Participants	—	—
Number of Participants With Post-transplant Infections Candidiasis (not invasive)	11 Participants	—	—
Number of Participants With Post-transplant Infections Sinusitis	11 Participants	—	—
Number of Participants With Post-transplant Infections Bacteremia, gram negative	9 Participants	—	—
Number of Participants With Post-transplant Infections CMV reactivation, no disease	9 Participants	—	—
Number of Participants With Post-transplant Infections BK virus, no disease	7 Participants	—	—
Number of Participants With Post-transplant Infections EBV-related lymphoproliferative disease	6 Participants	—	—
Number of Participants With Post-transplant Infections BK virus, hemorrhagic cystitis	5 Participants	—	—
Number of Participants With Post-transplant Infections Adenovirus disease	5 Participants	—	—
Number of Participants With Post-transplant Infections Infection with normal ANC - grade 3	5 Participants	—	—
Number of Participants With Post-transplant Infections Norovirus	5 Participants	—	—
Number of Participants With Post-transplant Infections Positive Galactomannan	5 Participants	—	—
Number of Participants With Post-transplant Infections Acute otitis media	4 Participants	—	—
Number of Participants With Post-transplant Infections HSV - mouth sores	4 Participants	—	—
Number of Participants With Post-transplant Infections EBV reactivation, no disease	4 Participants	—	—
Number of Participants With Post-transplant Infections Pneumonia	3 Participants	—	—
Number of Participants With Post-transplant Infections Varicella zoster	3 Participants	—	—
Number of Participants With Post-transplant Infections Candidiasis (invasive)	2 Participants	—	—
Number of Participants With Post-transplant Infections CMV, GI disease/ encephalitis	2 Participants	—	—
Number of Participants With Post-transplant Infections Disseminated aspergillus	2 Participants	—	—
Number of Participants With Post-transplant Infections Methicillin-Resistant Staph Aureus	2 Participants	—	—
Number of Participants With Post-transplant Infections Rotavirus	2 Participants	—	—
Number of Participants With Post-transplant Infections Pneumonia - fungal (non-aspergillus)	1 Participants	—	—
Number of Participants With Post-transplant Infections Influenza	1 Participants	—	—
Number of Participants With Post-transplant Infections Parvovirus B19 (low level)	1 Participants	—	—
Number of Participants With Post-transplant Infections Sapovirus	1 Participants	—	—
Number of Participants With Post-transplant Infections Possible respiratory infection (rhizomucor)	1 Participants	—	—

SECONDARY outcome

Timeframe: 5 years

Outcome measures

Measure	T Cell Depletion Using CliniMACS® n=52 Participants Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.	Matched Unrelated Donor Cohort	Matched Unrelated Donor Cohort Number of recipients alive following bone marrow transplant for non-malignant disease.
Number of Participants With EBV-related Post Transplant Lymphoproliferative Disorder (PTLD)	6 Participants	—	—

SECONDARY outcome

Timeframe: 5 years

Population: Of the 43 recipients in the mismatched related donor cohort, 24 of those had leukemia. No recipients in the matched unrelated donor cohort had leukemia.

Outcome measures

Measure	T Cell Depletion Using CliniMACS® n=24 Participants Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.	Matched Unrelated Donor Cohort	Matched Unrelated Donor Cohort Number of recipients alive following bone marrow transplant for non-malignant disease.
Number of Participants With Post-transplant Leukemia Relapse	5 Participants	—	—

SECONDARY outcome

Timeframe: 2 year

Population: Those who died due to disease relapse are not included in the analyzed population for that time point.

Transplant-related mortality includes death due to regimen-related toxicity or GVHD (all causes other than disease relapse). Those who died due to disease relapse are not included in the analyzed population for that time point.

Outcome measures

Measure	T Cell Depletion Using CliniMACS® n=52 Participants Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.	Matched Unrelated Donor Cohort	Matched Unrelated Donor Cohort Number of recipients alive following bone marrow transplant for non-malignant disease.
Number of Participants With Transplant-related Mortality Day 100	1 Participants	—	—
Number of Participants With Transplant-related Mortality 1 year	9 Participants	—	—
Number of Participants With Transplant-related Mortality 2 years	11 Participants	—	—

SECONDARY outcome

Timeframe: 1 year

Outcome measures

Measure	T Cell Depletion Using CliniMACS® n=52 Participants Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.	Matched Unrelated Donor Cohort	Matched Unrelated Donor Cohort Number of recipients alive following bone marrow transplant for non-malignant disease.
Number of Participants With Transplant-related Toxicities Thrombotic Microangiopathy	8 Participants	—	—
Number of Participants With Transplant-related Toxicities Idiopathic Pneumonia Syndrome	3 Participants	—	—
Number of Participants With Transplant-related Toxicities Veno-occlusive Disease	1 Participants	—	—

SECONDARY outcome

Timeframe: 2 years

Population: Subjects at least 2 years after transplant are evaluable for 2 year overall survival.

Outcome measures

Measure	T Cell Depletion Using CliniMACS® n=17 Participants Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.	Matched Unrelated Donor Cohort n=13 Participants	Matched Unrelated Donor Cohort n=7 Participants Number of recipients alive following bone marrow transplant for non-malignant disease.
Overall Survival	9 Participants	9 Participants	6 Participants

SECONDARY outcome

Timeframe: Length of the trial (5 years)

For mismatched related donors, the target cell dose after processing is >/= 20 x 10^6 CD34+ cells/kg patient body weight, but >/= 8 x 10^6 is acceptable.

For unrelated donors the target cell dose after processing is >/= 10 x 10^6 CD34+ cells/kg patient body weight, but >/= 4 x 10^6 is acceptable.

The target T cell dose is </= 3 x 10^4 CD3+ cells/ kg.

Outcome measures

Measure	T Cell Depletion Using CliniMACS® n=43 Participants Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.	Matched Unrelated Donor Cohort n=9 Participants	Matched Unrelated Donor Cohort Number of recipients alive following bone marrow transplant for non-malignant disease.
Device Performance: Dose of CD34+ Cells and CD3+ Cells Given x 10^6 CD34+ cells/ kg	20.26 cells/ kg Interval 8.78 to 25.03	15.16 cells/ kg Interval 11.06 to 23.33	—
Device Performance: Dose of CD34+ Cells and CD3+ Cells Given x 10^4 CD3+ cells/ kg	0.02 cells/ kg Interval 0.0 to 1.1	0.3 cells/ kg Interval 0.0 to 0.5	—

Adverse Events

T Cell Depletion Using CliniMACS®

Serious events: 45 serious events

Other events: 33 other events

Deaths: 15 deaths

Serious adverse events

Measure	T Cell Depletion Using CliniMACS® n=52 participants at risk Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.
General disorders Fever	61.5% 32/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Infections and infestations HHV-6 Reactivation	17.3% 9/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Immune system disorders Graft vs. Host disease	17.3% 9/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Blood and lymphatic system disorders Thrombotic microangiopathy	11.5% 6/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Gastrointestinal disorders Acute gastroenteritis/ diarrhea	9.6% 5/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Infections and infestations CMV reactivation	7.7% 4/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Infections and infestations EBV-related lymphoproliferative disease	7.7% 4/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Infections and infestations Pneumonia	7.7% 4/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Infections and infestations Infection w/ unknown absolute neutrophil count (ANC)	5.8% 3/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Respiratory, thoracic and mediastinal disorders Hypoxia	5.8% 3/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Renal and urinary disorders Hemorrhagic cystitis	5.8% 3/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Relapse	7.7% 2/26 • From the start of the conditioning regimen for transplant until 1 year after transplant
Blood and lymphatic system disorders Decreasing donor chimerism	3.8% 2/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Infections and infestations Infection - grade 4	3.8% 2/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Nervous system disorders Seizures	3.8% 2/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Respiratory, thoracic and mediastinal disorders Viral upper respiratory infection	3.8% 2/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Renal and urinary disorders Renal failure	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Renal and urinary disorders Renal & Urinary disorder - grade 3	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Gastrointestinal disorders Pneumoatosis Intestinalis	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Cardiac disorders Pericardial effusion	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Gastrointestinal disorders Mucositis/ dehydration	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Blood and lymphatic system disorders Leukopenia/ Neutropenia - grade 3	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
General disorders Infusion reaction	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
General disorders Hypothermia	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Vascular disorders Hypertension	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Respiratory, thoracic and mediastinal disorders Pulmonary/ Upper Respiratory- other	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Blood and lymphatic system disorders Graft failure	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Infections and infestations Infection - eye	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Metabolism and nutrition disorders Dehydration with hypernatremia	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Respiratory, thoracic and mediastinal disorders Aspiration	1.9% 1/52 • From the start of the conditioning regimen for transplant until 1 year after transplant

Other adverse events

Measure	T Cell Depletion Using CliniMACS® n=52 participants at risk Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device. CliniMACS® (T cell depletion): Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.
Respiratory, thoracic and mediastinal disorders Hypoxia - grade 3	26.9% 14/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Skin and subcutaneous tissue disorders Rash - grade 3	9.6% 5/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Nervous system disorders Seizures - grade 3	9.6% 5/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Metabolism and nutrition disorders Hypokalemia - grade 4	7.7% 4/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Respiratory, thoracic and mediastinal disorders Hypoxia - grade 4	7.7% 4/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Renal and urinary disorders Renal and Urinary disorder - grade 3	7.7% 4/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Blood and lymphatic system disorders Thrombotic microangiopathy - grade 4	7.7% 4/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Blood and lymphatic system disorders Thrombotic microangiopathy - grade 3	7.7% 4/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Investigations Elevated ALT - grade 4	5.8% 3/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Vascular disorders Hypertension - grade 4	5.8% 3/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Respiratory, thoracic and mediastinal disorders Idiopathic pneumonia syndrome	5.8% 3/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Nervous system disorders Posterior Reversible Encephalopathy Syndrome	5.8% 3/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Renal and urinary disorders Renal disorder - grade 4	5.8% 3/52 • From the start of the conditioning regimen for transplant until 1 year after transplant
Vascular disorders Thrombosis - grade 3 (catheter-related)	5.8% 3/52 • From the start of the conditioning regimen for transplant until 1 year after transplant

Additional Information

Dr. Andrew Gilman

PRA Health Sciences

Phone: 704-615-2744

Email: gilmanandy@prahs.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place