Adoptive Immunotherapy of High Risk Acute Myeloblastic Leukemia Patients Using Haploidentical Kir Ligand-mismatched Natural Killer Cells

NCT ID: NCT00799799

Last Updated: 2009-09-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2009-12-31

Brief 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.

Conditions

Myeloblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NK

patient treated as per protocol

Group Type: EXPERIMENTAL

NK cells

Intervention Type: BIOLOGICAL

NK cells infusion after immunosuppressive chemotherapy

Interventions

NK cells

NK cells infusion after immunosuppressive chemotherapy

Intervention Type: BIOLOGICAL

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Bologna

OTHER

Sponsor Role: lead

Responsible Party

Institute of Hematology "L. & A. Seragnoli" - University of Bologna

Locations

Institute of Hematology "L. & A. Seragnoli"

Bologna, Bo, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Roberto M Lemoli, MD

Role: CONTACT

roberto.lemoli@unibo.it

+39 051 636 ext. 3680

Antonio Curti, MD

Role: CONTACT

antonio.curti2@unibo.it

+39 051 636 ext. 3680

References

Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, Martelli MF, Velardi A. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002 Mar 15;295(5562):2097-100. doi: 10.1126/science.1068440.

Reference Type: BACKGROUND

PMID: 11896281 (View on PubMed)

Curti A, Ruggeri L, D'Addio A, Bontadini A, Dan E, Motta MR, Trabanelli S, Giudice V, Urbani E, Martinelli G, Paolini S, Fruet F, Isidori A, Parisi S, Bandini G, Baccarani M, Velardi A, Lemoli RM. Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood. 2011 Sep 22;118(12):3273-9. doi: 10.1182/blood-2011-01-329508. Epub 2011 Jul 25.

Reference Type: DERIVED

PMID: 21791425 (View on PubMed)

Other Identifiers

NK TRIAL

Identifier Type: -

Identifier Source: org_study_id