Trial Outcomes & Findings for Haploidentical Transplant With NK Cell Infusion for Pediatric Acute Leukemia and Solid Tumors (NCT NCT00582816)

Last Updated: 2019-12-09

Results Overview

Skin Grade III: Stage 0-4 GVHD, where 0 is no rash and 4 is generalized erythroderma with bullous formation and/or with desquamation Grade IV: Stage 4 GVHD, generalized erythroderma with bullous formation and/or with desquamation GI (diarrhea) Grade III: Stage 2-4 GVHD, where 2 is \> 1000 mL/day but ≤ 1500 mL/day or 556-833 mL/m2, and 4 is severe abdominal pain +/- ileus or stool with frank blood or melena Grade IV: Stage 0-4 GVHD, where 0 is \< 500 mL/day or 280 mL/m2, and 4 is severe abdominal pain +/- ileus or stool with frank blood or melena Overall: Grade III: Grade III Skin and/or GI as well as bilirubin 3.1-15 mg/dl Grade IV: Grade IV Skin and/or GI as well as bilirubin \> 15 mg/dl

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

9 participants

Primary outcome timeframe

Day 100

Results posted on

2019-12-09

Participant Flow

This study enrolled patients with relapsed acute leukemia and very high-risk solid tumors. The last subject was enrolled in October 2013.

Participant milestones

Participant milestones
Measure	Haploidentical Transplant With NK Cell Infusion Patients underwent a standard pre-transplant evaluation, but will also had blood drawn to evaluate their HLA class I killer immunoglobulin-like receptor (KIR) ligand typing. Parents underwent KIR genotyping and phenotyping, and a donor was selected based on which parent showed the greatest degree of KIR receptor-ligand mismatching. When the donor had been selected he/she underwent a peripheral blood stem cell (PBSC) collection utilizing G-CSF and GM-CSF for stem cell mobilization. The PBSC collection was performed utilizing standard procedures. The PBSC was then be processed in the UW BMT Laboratory in order to deplete the graft of T cells. This was accomplished using the CliniMACS cell separation system. T cell depletion is a standard procedure for patients receiving haploidentical stem cell grafts. The resulting stem cell product were analyzed for T cell, stem cell and NK cell content. Clinimacs Cell Separation System: Depletion of T-cells
Overall Study STARTED	9
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Haploidentical Transplant With NK Cell Infusion Patients underwent a standard pre-transplant evaluation, but will also had blood drawn to evaluate their HLA class I killer immunoglobulin-like receptor (KIR) ligand typing. Parents underwent KIR genotyping and phenotyping, and a donor was selected based on which parent showed the greatest degree of KIR receptor-ligand mismatching. When the donor had been selected he/she underwent a peripheral blood stem cell (PBSC) collection utilizing G-CSF and GM-CSF for stem cell mobilization. The PBSC collection was performed utilizing standard procedures. The PBSC was then be processed in the UW BMT Laboratory in order to deplete the graft of T cells. This was accomplished using the CliniMACS cell separation system. T cell depletion is a standard procedure for patients receiving haploidentical stem cell grafts. The resulting stem cell product were analyzed for T cell, stem cell and NK cell content. Clinimacs Cell Separation System: Depletion of T-cells
Overall Study Engraftment Failure	3

Baseline Characteristics

Haploidentical Transplant With NK Cell Infusion for Pediatric Acute Leukemia and Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Haploidentical Transplant With NK Cell Infusion n=9 Participants Patients underwent a standard pre-transplant evaluation, but will also had blood drawn to evaluate their HLA class I killer immunoglobulin-like receptor (KIR) ligand typing. Parents underwent KIR genotyping and phenotyping, and a donor was selected based on which parent showed the greatest degree of KIR receptor-ligand mismatching. When the donor had been selected he/she underwent a peripheral blood stem cell (PBSC) collection utilizing G-CSF and GM-CSF for stem cell mobilization. The PBSC collection was performed utilizing standard procedures. The PBSC was then be processed in the UW BMT Laboratory in order to deplete the graft of T cells. This was accomplished using the CliniMACS cell separation system. T cell depletion is a standard procedure for patients receiving haploidentical stem cell grafts. The resulting stem cell product were analyzed for T cell, stem cell and NK cell content. Clinimacs Cell Separation System: Depletion of T-cells
Age, Categorical <=18 years	9 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	2 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 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	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	8 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
Region of Enrollment United States	9 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 100

Outcome measures

Outcome measures
Measure	Haploidentical Transplant With NK Cell Infusion n=9 Participants Patients underwent a standard pre-transplant evaluation, but will also had blood drawn to evaluate their HLA class I killer immunoglobulin-like receptor (KIR) ligand typing. Parents underwent KIR genotyping and phenotyping, and a donor was selected based on which parent showed the greatest degree of KIR receptor-ligand mismatching. When the donor had been selected he/she underwent a peripheral blood stem cell (PBSC) collection utilizing G-CSF and GM-CSF for stem cell mobilization. The PBSC collection was performed utilizing standard procedures. The PBSC was then be processed in the UW BMT Laboratory in order to deplete the graft of T cells. This was accomplished using the CliniMACS cell separation system. T cell depletion is a standard procedure for patients receiving haploidentical stem cell grafts. The resulting stem cell product were analyzed for T cell, stem cell and NK cell content. Clinimacs Cell Separation System: Depletion of T-cells
Grade III or IV GVHD Grade III GVHD - Skin	3 participants
Grade III or IV GVHD Grade IV GVHD - GI	2 participants
Grade III or IV GVHD Grade III GVHD - GI	1 participants
Grade III or IV GVHD Overall Grade III GVHD	2 participants
Grade III or IV GVHD Overall Grade IV GVHD	2 participants

PRIMARY outcome

Timeframe: 28 days

Utilize non-myeloablative conditioning regimen in the haploidentical transplant setting. Primary engraftment failure: failure to achieve ANC of ≥500/uL prior to day +28 Late engraftment failure: Initial engraftment achieved with ANC ≥500/uL by day +28 followed by loss of graft Autologous Cells Infused: achieved hematologic recovery following infusions of autologous stem cells Second Haploidentical Transplant: re-transplantation utilizing an alternative haploidentical donor

Outcome measures

Outcome measures
Measure	Haploidentical Transplant With NK Cell Infusion n=9 Participants Patients underwent a standard pre-transplant evaluation, but will also had blood drawn to evaluate their HLA class I killer immunoglobulin-like receptor (KIR) ligand typing. Parents underwent KIR genotyping and phenotyping, and a donor was selected based on which parent showed the greatest degree of KIR receptor-ligand mismatching. When the donor had been selected he/she underwent a peripheral blood stem cell (PBSC) collection utilizing G-CSF and GM-CSF for stem cell mobilization. The PBSC collection was performed utilizing standard procedures. The PBSC was then be processed in the UW BMT Laboratory in order to deplete the graft of T cells. This was accomplished using the CliniMACS cell separation system. T cell depletion is a standard procedure for patients receiving haploidentical stem cell grafts. The resulting stem cell product were analyzed for T cell, stem cell and NK cell content. Clinimacs Cell Separation System: Depletion of T-cells
Engraftment Failure Primary Engraftment Failure	2 participants
Engraftment Failure Late Engraftment Failure	1 participants
Engraftment Failure Autologous Cells Infused	2 participants
Engraftment Failure Second Haploidentical Transplant	1 participants

PRIMARY outcome

Timeframe: 28 days

Utilize non-myeloablative conditioning regimen in the haploidentical transplant setting. Engraftment is defined as achieving an absolute neutrophil count ≥ 500 by 28 days post-transplant; platelets and red blood cells will also be measured up to 28 days: * Neutrophils: ≥500/uL for 3 days * Platelets: ≥20 K/uL for 3 days without transfusion * Red blood cells: the date of the last RBC transfusion after achieving transfusion independence Results are reported as number of days until engraftment criteria was met, per neutrophil, platelet and red blood cell measurements, above.

Outcome measures

Outcome measures
Measure	Haploidentical Transplant With NK Cell Infusion n=7 Participants Patients underwent a standard pre-transplant evaluation, but will also had blood drawn to evaluate their HLA class I killer immunoglobulin-like receptor (KIR) ligand typing. Parents underwent KIR genotyping and phenotyping, and a donor was selected based on which parent showed the greatest degree of KIR receptor-ligand mismatching. When the donor had been selected he/she underwent a peripheral blood stem cell (PBSC) collection utilizing G-CSF and GM-CSF for stem cell mobilization. The PBSC collection was performed utilizing standard procedures. The PBSC was then be processed in the UW BMT Laboratory in order to deplete the graft of T cells. This was accomplished using the CliniMACS cell separation system. T cell depletion is a standard procedure for patients receiving haploidentical stem cell grafts. The resulting stem cell product were analyzed for T cell, stem cell and NK cell content. Clinimacs Cell Separation System: Depletion of T-cells
Number of Days Until Engraftment Criteria Were Met Neutrophils	18 days Interval 14.0 to 20.0
Number of Days Until Engraftment Criteria Were Met Platelets	16 days Interval 10.0 to 21.0
Number of Days Until Engraftment Criteria Were Met Red Blood Cells	16 days Interval 8.0 to 22.0

PRIMARY outcome

Timeframe: 100 days post-transplant

Population: Death Prior to Day +100

Mortality rate at 100 days post-transplant.

Outcome measures

Outcome measures
Measure	Haploidentical Transplant With NK Cell Infusion n=9 Participants Patients underwent a standard pre-transplant evaluation, but will also had blood drawn to evaluate their HLA class I killer immunoglobulin-like receptor (KIR) ligand typing. Parents underwent KIR genotyping and phenotyping, and a donor was selected based on which parent showed the greatest degree of KIR receptor-ligand mismatching. When the donor had been selected he/she underwent a peripheral blood stem cell (PBSC) collection utilizing G-CSF and GM-CSF for stem cell mobilization. The PBSC collection was performed utilizing standard procedures. The PBSC was then be processed in the UW BMT Laboratory in order to deplete the graft of T cells. This was accomplished using the CliniMACS cell separation system. T cell depletion is a standard procedure for patients receiving haploidentical stem cell grafts. The resulting stem cell product were analyzed for T cell, stem cell and NK cell content. Clinimacs Cell Separation System: Depletion of T-cells
Mortality Rate	1 participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: Blood samples were not collected uniformly as many patients developed GVHD, requiring treatment with steroids. Once steroids were initiated the results of this testing became uninterpretable. No data was collected towards this outcome measure.

Natural Killer (NK) cell expression levels will be explored. Blood samples will be collected at months 1, 2, 3, 6, 9, and 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 60

NK cells express killer-cell immunoglobulin-like receptors (KIR) and have cytotoxic activity. The association between NK cell cytotoxicity over time and KIR genotypes will be examined. Blood samples will be collected at months 1, 2, 3, 6, 9, and 12.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 12 months

NK cell KIR expression over time will be examined. Blood samples will be collected at months 1, 2, 3, 6, 9, and 12.

Outcome measures

Outcome data not reported

Adverse Events

Haploidentical Transplant With NK Cell Infusion

Serious events: 8 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Haploidentical Transplant With NK Cell Infusion n=9 participants at risk Patients underwent a standard pre-transplant evaluation, but will also had blood drawn to evaluate their HLA class I killer immunoglobulin-like receptor (KIR) ligand typing. Parents underwent KIR genotyping and phenotyping, and a donor was selected based on which parent showed the greatest degree of KIR receptor-ligand mismatching. When the donor had been selected he/she underwent a peripheral blood stem cell (PBSC) collection utilizing G-CSF and GM-CSF for stem cell mobilization. The PBSC collection was performed utilizing standard procedures. The PBSC was then be processed in the UW BMT Laboratory in order to deplete the graft of T cells. This was accomplished using the CliniMACS cell separation system. T cell depletion is a standard procedure for patients receiving haploidentical stem cell grafts. The resulting stem cell product were analyzed for T cell, stem cell and NK cell content. Clinimacs Cell Separation System: Depletion of T-cells
Infections and infestations Grade 3 infection	44.4% 4/9 • Number of events 5 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Grade 3 anorexia	33.3% 3/9 • Number of events 3 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Grade 3 diarrhea	22.2% 2/9 • Number of events 2 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Grade 3 GVHD	22.2% 2/9 • Number of events 2 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Nervous system disorders Grade 2 seizure	22.2% 2/9 • Number of events 2 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Grade 4 engraftment failure possibly from CMV riemia or inadequate stem cell dose	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Grade 4 engraftment failure	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
General disorders Death	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Grade 3 dehydration	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Gastrointestinal disorders Grade 2 diarrhea	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
General disorders Grade 1 fever	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
General disorders Grade 3 fever	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Grade 2 acute GVHD	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Skin and subcutaneous tissue disorders Grade 3 skin GVHD	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Blood and lymphatic system disorders Grade 4 graft rejection	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Metabolism and nutrition disorders Grade 3 hyponatremia	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Infections and infestations Grade 4 infection	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
Nervous system disorders Grade 1 leukoencephalopathy	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.
General disorders Grade 2 pain	11.1% 1/9 • Number of events 1 • Adverse event data were collected for up to 3 years. Adverse events were routinely determined to have occurred by regular investigator assessment and regular laboratory testing.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Ken DeSantes

University of Wisconsin Carbone Cancer Center

Phone: 608-263-8563

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place