Adoptive Immunotherapy of High Risk Acute Myeloblastic Leukemia Patients Using Haploidentical Kir Ligand-Mismatched Natural Killer Cells - Full Text View

Sponsored by:	University of Bologna
Information provided by:	University of Bologna
ClinicalTrials.gov Identifier:	NCT00799799

Purpose

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	Intervention	Phase
Myeloblastic Leukemia	Biological: NK cells	Phase I

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Historical Control, Single Group Assignment, Safety Study
Official Title:	Adoptive Immunotherapy of High Risk Acute Myeloblastic Leukemia Patients Using Haploidentical Kir Ligand-Mismatched Natural Killer Cells

Further study details as provided by University of Bologna:

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 [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]
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 [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate the microchimerism of AML patients receiving haploidentical human NK cells for adoptive immunotherapy [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]
To evaluate, in vitro and in vivo, the antitumor activity of haploidentical NK cells infused in AML patients [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]
To assess the percentage of patients entering complete remission (CR) after the reinfusion of highly purified haploidentical NK cells [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]
To assess the disease-free and overall survival of AML patients infused with haploidentical NK cells [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]
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 [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	15
Study Start Date:	October 2005
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
NK: Experimental patient treated as per protocol	Biological: NK cells NK cells infusion after immunosuppressive chemotherapy

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00799799

Contacts

Contact: Roberto M Lemoli, MD	+39 051 636 ext 3680	roberto.lemoli@unibo.it
Contact: Antonio Curti, MD	+39 051 636 ext 3680	antonio.curti2@unibo.it

Locations

Italy, Bo
Institute of Hematology "L. & A. Seragnoli"	Recruiting
Bologna, Bo, Italy, 40138

Sponsors and Collaborators

University of Bologna

More Information

Publications:

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.

Responsible Party:	Institute of Hematology "L. & A. Seragnoli" - University of Bologna ( prof. Roberto M. Lemoli )
Study ID Numbers:	NK TRIAL
Study First Received:	November 28, 2008
Last Updated:	December 2, 2008
ClinicalTrials.gov Identifier:	NCT00799799
Health Authority:	Italy: Ethics Committee

Keywords provided by University of Bologna:

Nk cells infusion
minimal residual disease in AML patients
trafficking of NK cells after infusion
cytolytic effects on leukemic cells

Study placed in the following topic categories:

Neoplasm, Residual
Leukemia
Acute myelogenous leukemia

Leukemia, Myeloid
Leukemia, Myeloid, Acute
Acute myelocytic leukemia

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on January 16, 2009