Haploidentical Transplant With NK Cell Infusion for Pediatric Acute Leukemia and Solid Tumors
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|ClinicalTrials.gov Identifier: NCT00582816|
Recruitment Status : Terminated (toxicity)
First Posted : December 28, 2007
Results First Posted : July 19, 2017
Last Update Posted : December 9, 2019
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|Condition or disease||Intervention/treatment||Phase|
|Leukemia Solid Tumors||Device: Clinimacs Cell Separation System Drug: conditioning chemotherapy Other: DLI||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Reduced Intensity Haploidentical Transplantation With NK Cell Infusion for Pediatric Acute Leukemia and High Risk Solid Tumors, BMT06407|
|Study Start Date :||August 2008|
|Actual Primary Completion Date :||August 2015|
|Actual Study Completion Date :||August 2015|
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.
Device: Clinimacs Cell Separation System
Depletion of T-cells
Drug: conditioning chemotherapy
Methylprednisolone, Equine ATG, Cyclosporine, Fludarabine, Melphalan, Thiotepa and Rituximab.
NK Cell selected DLI
- Grade III or IV GVHD [ Time Frame: Day 100 ]
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
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
- Engraftment Failure [ Time Frame: 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
- Number of Days Until Engraftment Criteria Were Met [ Time Frame: 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.
- Mortality Rate [ Time Frame: 100 days post-transplant ]Mortality rate at 100 days post-transplant.
- NK Expression Levels [ Time Frame: Up to 12 months ]Natural Killer (NK) cell expression levels will be explored. Blood samples will be collected at months 1, 2, 3, 6, 9, and 12.
- Association Between Parental KIR Genotypes and NK Cell Cytotoxicities [ Time Frame: 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.
- Analysis of NK Cell KIR Expression Over Time [ Time Frame: 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.
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|Ages Eligible for Study:||6 Months to 25 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Solid tumors that have failed auto transplant or are ineligible to receive auto transplant
- Relapsed AML in 1st relapse or 2nd or 3rd CR
- Relapsed ALL if they fail to attain an initial remission or if they relapse within 1 year following the discontinuation of chemotherapy.
- Greater than or equal to 6 months and <26 years old
- Suitable haploidentical donor available
- Leukemia with >25% blasts in bone marrow at the time of admission to the HSCT unit.
- Serum bilirubin >3 mg/dl
- GFR <40 ml/min/1.73 mw
- Cardiac left ventricular ejection fraction <40%
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00582816
|United States, Wisconsin|
|Kenneth DeSantes., MD|
|Madison, Wisconsin, United States, 53972|
|Principal Investigator:||Kenneth DeSantes, M.D.||University of Wisconsin, Madison|
|Responsible Party:||University of Wisconsin, Madison|
|Other Study ID Numbers:||
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 )
|First Posted:||December 28, 2007 Key Record Dates|
|Results First Posted:||July 19, 2017|
|Last Update Posted:||December 9, 2019|
|Last Verified:||July 2017|
Recurrent or Refractory Leukemia or Solid Tumors in Pediatrics
Neoplasms by Histologic Type