Haploidentical NK-cell Infusion in Acute Myeloid Leukemia

NCT ID: NCT01947322

Last Updated: 2017-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-31
• Study Completion Date: 2016-01-31

Brief Summary

Leukemia cells can be killed by natural killer (NK) from HLA-I mismatched donor. The proposed study plans to realize an adoptive anti-leukaemic immunotherapy by infusion of HLA-I mismatched NK cells to treat poor prognosis acute myeloid leukemia patients. NK cells will be selected from HLA mismatch familial donor peripheral mononuclear cells by purification protocol. Before NK-infusion, patients received immunosuppressive chemotherapy.

Detailed Description

NK cell-mediated cytotoxity is regulated by signals provided by surface inhibitory and activating receptors. Target cells will be killed in the absence of interaction between NK inhibitory receptors and their ligands (HLA class I molecules) on the target cells. The proposed phase I/II study plans to realize an adoptive anti-leukaemic immunotherapy by infusion of haploidentical HLA-I mismatched NK cells to treat poor prognosis AML patients. Familial donors of NK cells will be selected according to their HLA typing in order to choose a donor with NK cells expressing at least one inhibitory receptor that can not recognize any HLA class I molecule on recipient cells. NK cells will be selected from donor peripheral mononuclear cells by a two step purification protocol (CD3 negative with subsequent CD56 positive selections). NK cells will be then activated ex vivo overnight in the presence of IL-2 before infusion. In vivo IL-2 injections will be performed for 14 days. Before NK-infusion, patients will be conditioned by a cytoreductive and immunosuppressive chemotherapy. An extensive biological study of NK cells will be performed in the recipient post-infusion, including chimerism analyses, phenotypic and functional tests in order to evaluate NK-cell expansion post-infusion and their capacity to mediate an antitumoral effect. Since donor NK cells have been selected for their potential graft versus host (GvH) and graft versus leukemia (GvL) reactivity, such approach might induce prolonged cytopenia due to a direct toxicity of NK cells against normal hematopoietic progenitors. The main goals of this study will be thus to evaluate (1) the hematological feasibility of allogeneic NK-cell infusion, (2) the expansion of the infused population, (3) an antitumoral effect mediated by this adoptive immunotherapy. This is an essential step before further development of such anti-tumoral immunotherapeutic approach, in leukemic patients but also in solid tumors that could be sensitive to an "NK-effect" (melanoma, kidney cancer).

This project includes 4 clinical departments and several laboratories of cellular therapy and immunology that have got an expertise in the field of Acute Myeloid Leukemia (AML), cellular therapy and NK-cell.

Conditions

Acute Myeloid Leukemia

Study Design

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

Study Groups

Allogenic NK cells infusion

Group Type: EXPERIMENTAL

Allogenic NK cells infusion

Intervention Type: DRUG

HLA Haploidentical selected NK cell infusion (one injection of 1x107/kg CD3-CD56+ cells) after chemotherapy associating fludarabine, cytosine arabinoside and cyclophosphamide.

Interventions

Allogenic NK cells infusion

HLA Haploidentical selected NK cell infusion (one injection of 1x107/kg CD3-CD56+ cells) after chemotherapy associating fludarabine, cytosine arabinoside and cyclophosphamide.

Intervention Type: DRUG

Other Intervention Names

cellular therapy

Eligibility Criteria

Exclusion Criteria

• Secondary AML.
• Previous autologous or allogeneic transplantation. Since the main objective of the study concerns the hematological toxicity, we decided to exclude patients with secondary AML or who had been previously transplanted because of their expected higher hematological toxicity.
• Patient with allogeneic transplant project
• HIV positive serology

2. Donor eligibility

• HLA haploidentical brother, sister, child (older than 18 years), father, sister, cousin, uncle, aunt.
• Donor with KIR ligand mismatch in the GvL direction
• Absence of contraindication for leukapheresis.
• Negative HIV1-2, HTLV-1-2, HBV, and HCV serology. Negative viral genomic screening for HTLV1-2 and HCV
• Written informed consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nathalie Dhedin, MD

Role: PRINCIPAL_INVESTIGATOR

APHP

Locations

Service d'Hématologie Clinique du Pr. Leblond- Hôpital Pitié salpêtrière

Paris, , France

Service d'Hématologie adultes du Pr. Hermine - Hôpital Necker Enfants Malades

Paris, , France

Service d'Hématologie oncologie du Pr. Mohty -Hôpital Saint Antoine

Paris, , France

Service d'Hématologie Clinique du Pr. Cordonnier-Hôpital Henri Mondor

Paris, , France

Countries

France

Other Identifiers

P070505

Identifier Type: -

Identifier Source: org_study_id