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

Leukemia Clinical Trial

Official title:

Reduced Intensity Haploidentical Transplantation With NK Cell Infusion for Pediatric Acute Leukemia and High Risk Solid Tumors, BMT06407

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00582816
• Other study ID #: BMT06407
• Secondary ID: H-2006-02972012-
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: August 2008
• Est. completion date: August 2015

Study information

• Verified date: July 2017
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 25 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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%

• HIV+

• Pregnant

Related Conditions & MeSH terms

• Leukemia
• Solid Tumors

Intervention

Device:
• Clinimacs Cell Separation System
Depletion of T-cells

Drug:
• conditioning chemotherapy
Methylprednisolone, Equine ATG, Cyclosporine, Fludarabine, Melphalan, Thiotepa and Rituximab.

Other:
• DLI
NK Cell selected DLI

Locations

Country	Name	City	State
United States	Kenneth DeSantes., MD	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	Miltenyi Biotec GmbH

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	Day 100
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	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: 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.	28 days
Primary	Mortality Rate	Mortality rate at 100 days post-transplant.	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.	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.	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.	Up to 12 months

External Links

•   University of Wisconsin Carbone Cancer Center