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Adoptive Immunotherapy of High Risk Acute Myeloblastic Leukemia Patients Using Haploidentical Kir Ligand-mismatched Natural Killer Cells
Conditions
Myeloblastic Leukemia
Conditions: official terms
Leukemia - Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
Nk cells infusion, minimal residual disease in AML patients, trafficking of NK cells after infusion, cytolytic effects on leukemic cells
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: NK cells
Type: Biological
Overall Status
Recruiting
Summary
AML patients with de-novo or secondary disease with age greater than 18 years not eligible for stem cell transplantation for medical contraindications, lack of donor or lack of stem cells,are eligible. Leukemias other than AML and M3 FAB subtype will be excluded from the study. Immunosuppressive chemotherapy prior to NK cell infusion will include: fludarabine and cyclophosphamide 4g/m2 (Flu/Cy). The therapy will be administered over 6 days on inpatient basis. Haploidentical NK cells will be selected from a steady-state large volume leukapheresis product from a suitable KIR ligand incompatible donor. Donor-recipients pairs will be selected on the basis of known KIR ligands. In particular, haploidentical donors will be included if present at least one allele mismatch at a class I locus among the following ones: HLA-C alleles with Asn77-Lys80, HLA-C alleles with Ser77-Asn80, HLA-Bw4 alleles. Immunomagnetic enrichment of NK cells will follow two subsequent steps: 1) depletion of CD3+ T cells followed by 2) positive selection of CD56+ NK cells. Contaminating CD3+ T cells will be carefully evaluated.
Detailed Description
When previously cryproserved NK cells are still available, further re-infusions may be performed, according to PI's evaluation. The number of remaining NK cells must be sufficient for the reinfusion of at least the minimum dose of cells (106/kg). At least two months should elapse between two consecutive infusion procedures.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:
- Signed informed consent.
- Performance Status ≥ 70% (Karnofsky score) or ≤ 2 (WHO).
- Age greater than 18 years.
- Availability of a KIR incompatible haploidentical donor.
- Adequate renal (serum creatinine < 2 mg/dl), pulmonary (Sat O2 ≥ 96%) and hepatic (ALT/AST < 2.5 x N) function.
- Patients enrolled in the protocol must have an autologous graft cryopreserved to be reinfused in case of severe myelosuppression induced by haploidentical NK cells. Back-up cells will be reinfused in case of ANC < 0.5 x 109/L at day + 40 from the start of immunosuppressive regimen.
Exclusion Criteria:
- Age < 18.
- People unable to give informed consent.
- HIV positivity.
- HCV positivity with high viral load.
- Intercurrent organ damage or medical problems that would interfere with therapy.
- Pregnant or nursing females.
- Current uncontrolled infection.
- No availability of a cryopreserved autologous stem cell graft to be reinfused in case of severe myelosuppression.
- Signs or symptoms of fluid retention (e.g. pleural effusion)
- Signed informed consent.
- Performance Status ≥ 70% (Karnofsky score) or ≤ 2 (WHO).
- Age greater than 18 years.
- Availability of a KIR incompatible haploidentical donor.
- Adequate renal (serum creatinine < 2 mg/dl), pulmonary (Sat O2 ≥ 96%) and hepatic (ALT/AST < 2.5 x N) function.
- Patients enrolled in the protocol must have an autologous graft cryopreserved to be reinfused in case of severe myelosuppression induced by haploidentical NK cells. Back-up cells will be reinfused in case of ANC < 0.5 x 109/L at day + 40 from the start of immunosuppressive regimen.
Exclusion Criteria:
- Age < 18.
- People unable to give informed consent.
- HIV positivity.
- HCV positivity with high viral load.
- Intercurrent organ damage or medical problems that would interfere with therapy.
- Pregnant or nursing females.
- Current uncontrolled infection.
- No availability of a cryopreserved autologous stem cell graft to be reinfused in case of severe myelosuppression.
- Signs or symptoms of fluid retention (e.g. pleural effusion)
Location
Institute of Hematology "L. & A. Seragnoli"
Bologna, Bo, Italy
Status: Recruiting
Start Date
October 2005
Completion Date
December 2009
Sponsors
University of Bologna
Source
University of Bologna
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
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