Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| H-2006-0297 | Other Identifier | UW IRB | |
| 2012-0661 | Other Identifier | UW IRB | |
| A536700 | Other Identifier | UW Madison | |
| SMPH\PEDIATRICS\PEDIATRICS | Other Identifier | UW Madison | |
| NCI-2011-00687 | Registry Identifier | NCI Trial ID |
Not provided
Not provided
Not provided
toxicity
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Miltenyi Biomedicine GmbH | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This study will assess the feasibility of utilizing a reduced intensity conditioning regimen, in the setting of haploidentical transplantation, for patients with recurrent acute lymphoblastic leukemia (ALL), AML and high risk or refractory solid tumors. In addition, the feasibility and safety of administering post-transplant NK cell infusions will be evaluated. Data obtained from this study will help determine the efficacy of allogeneic HSCT in the treatment of pediatric sarcomas and add to the small body of literature utilizing haploidentical HSCT to treat acute leukemia in pediatric patients. This study will also further elucidate the role of NK cells in mediating a graft vs. tumor effect in allogeneic HSCT. The main benefit to society is that this study will explore a novel therapy for children with highly refractory cancer who are felt to be incurable with conventional approaches. If feasibility is demonstrated, and there is evidence of anti-tumor activity, then this will open up a new area of clinical research to better define the efficacy of this approach for specific childhood malignancies.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | patients will undergo a standard pre-transplant evaluation, but will also have blood drawn to evaluate their HLA class I killer immunoglobulin-like receptor (KIR) ligand typing. Parents will undergo KIR genotyping and phenotyping, and a donor will be selected based on which parent shows the greatest degree of KIR receptor-ligand mismatching. Once the donor has been selected he/she will undergo a peripheral blood stem cell (PBSC) collection utilizing G-CSF and GM-CSF for stem cell mobilization. The PBSC collection will be performed utilizing standard procedures. The PBSC will then be processed in the UW BMT Laboratory in order to deplete the graft of T cells. This will be 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 will be analyzed for T cell, stem cell and NK cell content. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Clinimacs Cell Separation System | Device | Depletion of T-cells |
| |
| conditioning chemotherapy |
| Measure | Description | Time Frame |
|---|---|---|
| Grade III or IV GVHD | 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 | Day 100 |
| Engraftment Failure | 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 | 28 days |
| Number of Days Until Engraftment Criteria Were Met | 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:
| 28 days |
| Mortality Rate | Mortality rate at 100 days post-transplant. | 100 days post-transplant |
| Measure | Description | Time Frame |
|---|---|---|
| NK Expression Levels | Natural Killer (NK) cell expression levels will be explored. Blood samples will be collected at months 1, 2, 3, 6, 9, and 12. | Up to 12 months |
| Association Between Parental KIR Genotypes and NK Cell Cytotoxicities |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Kenneth DeSantes, M.D. | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kenneth DeSantes., MD | Madison | Wisconsin | 53972 | United States |
Not provided
| Label | URL |
|---|---|
| University of Wisconsin Carbone Cancer Center | View source |
Not provided
Not provided
This study enrolled patients with relapsed acute leukemia and very high-risk solid tumors. The last subject was enrolled in October 2013.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Grade III or IV GVHD | 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 | Posted | Number | participants | Day 100 |
|
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Grade 3 infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
Not provided
This study involved a small patient cohort; blood samples were to be collected towards the secondary outcome measures. Unfortunately, participants whose blood samples were collected developed GVHD and the tests became uninterpretable.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ken DeSantes | University of Wisconsin Carbone Cancer Center | 608-263-8563 | kbdesantes@pediatrics.wisc.edu |
Not provided
| ID | Term |
|---|---|
| D007938 | Leukemia |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Drug |
Methylprednisolone, Equine ATG, Cyclosporine, Fludarabine, Melphalan, Thiotepa and Rituximab. |
|
| DLI | Other | NK Cell selected DLI |
|
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.
| Day 60 |
| Analysis of NK Cell KIR Expression Over Time | NK cell KIR expression over time will be examined. Blood samples will be collected at months 1, 2, 3, 6, 9, and 12. | Up to 12 months |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Engraftment Failure | 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 | Posted | Number | participants | 28 days |
|
|
|
| Primary | Number of Days Until Engraftment Criteria Were Met | 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:
| Posted | Median | Full Range | days | 28 days |
|
|
|
| Primary | Mortality Rate | Mortality rate at 100 days post-transplant. | Death Prior to Day +100 | Posted | Number | participants | 100 days post-transplant |
|
|
|
| Secondary | NK Expression Levels | Natural Killer (NK) cell expression levels will be explored. Blood samples will be collected at months 1, 2, 3, 6, 9, and 12. | 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. | Posted | Up to 12 months |
|
|
| Secondary | Association Between Parental KIR Genotypes and NK Cell Cytotoxicities | 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. | 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. | Posted | Day 60 |
|
|
| Secondary | Analysis of NK Cell KIR Expression Over Time | NK cell KIR expression over time will be examined. Blood samples will be collected at months 1, 2, 3, 6, 9, and 12. | 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. | Posted | Up to 12 months |
|
|
| 8 |
| 9 |
| 0 |
| 9 |
| Grade 3 anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 3 diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 3 GVHD | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 2 seizure | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 4 engraftment failure possibly from CMV riemia or inadequate stem cell dose | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 4 engraftment failure | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Death | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 3 dehydration | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 2 diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 1 fever | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 3 fever | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 2 acute GVHD | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 3 skin GVHD | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 4 graft rejection | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 3 hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 4 infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Grade 1 leukoencephalopathy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Grade 2 pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
Not provided
Not provided
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Title | Measurements |
|---|---|
|
| Second Haploidentical Transplant |
|
| Title | Measurements |
|---|---|
|