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

NCT00799799 | Unknown Phase 1 DMC

• 1 other identifier: NK TRIAL
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Myeloblastic Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

Study Arms (1)

NK

EXPERIMENTAL

patient treated as per protocol

Biological: NK cells

Interventions

NK cells BIOLOGICAL

NK cells infusion after immunosuppressive chemotherapy

NK

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Bologna: lead

Study Sites (1)

Institute of Hematology "L. & A. Seragnoli"

Bologna, Bo, 40138, Italy

RECRUITING

Related Publications (2)

• 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.

  PMID: 11896281 BACKGROUND

• 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.

  PMID: 21791425 DERIVED

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Roberto M Lemoli, MD

CONTACT

+39 051 636; roberto.lemoli@unibo.it

Antonio Curti, MD

CONTACT

+39 051 636; antonio.curti2@unibo.it

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 28, 2008
• First Posted: December 1, 2008
• Study Start: October 1, 2005
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: September 24, 2009

Record last verified: 2009-09

Locations

IT (1)