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

Sponsor

University of Bologna (Other)

Overall Status

Unknown status

CT.gov ID

NCT00799799

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myeloblastic Leukemia	Biological: NK cells	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2005

Anticipated Primary Completion Date :

Dec 1, 2009

Anticipated Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NK patient treated as per protocol	Biological: NK cells NK cells infusion after immunosuppressive chemotherapy

Arm

Intervention/Treatment

Experimental: NK

patient treated as per protocol

Biological: NK cells

NK cells infusion after immunosuppressive chemotherapy

Outcome Measures

Primary Outcome Measures

To assess the feasibility of the selection and reinfusion of 5x10E6 haploidentical natural killer (NK) cells /Kg of body weight (target cell dose) in at least 40% of adult patients with active acute myeloblastic leukemia (AML) entering the study [every 6 months]
To assess the feasibility of the reinfusion of the minimum accepted cell dose (1x10E6 haploidentical NK cells /Kg) in all patients enrolled into the protocol [every 6 months]

Secondary Outcome Measures

To evaluate the microchimerism of AML patients receiving haploidentical human NK cells for adoptive immunotherapy [every 6 months]
To evaluate, in vitro and in vivo, the antitumor activity of haploidentical NK cells infused in AML patients [every 6 months]
To assess the percentage of patients entering complete remission (CR) after the reinfusion of highly purified haploidentical NK cells [every 6 months]
To assess the disease-free and overall survival of AML patients infused with haploidentical NK cells [every 6 months]
To assess the safety of infusion of haploidentical NK cells, following immunosuppressive chemotherapy, considered as the incidence of adverse event (graded according to WHO) and clinically significant abnormal laboratory values following reinfusion [every 6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)