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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2009 by University of Bologna.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of Bologna
ClinicalTrials.gov Identifier:
NCT00799799
First received: November 28, 2008
Last updated: September 23, 2009
Last verified: September 2009
  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 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adoptive Immunotherapy of High Risk Acute Myeloblastic Leukemia Patients Using Haploidentical Kir Ligand-mismatched Natural Killer Cells

Resource links provided by NLM:


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

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.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Institute of Hematology "L. & A. Seragnoli" Recruiting
Bologna, Bo, Italy, 40138
Sponsors and Collaborators
University of Bologna
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: prof. Roberto M. Lemoli, Institute of Hematology "L. & A. Seragnoli" - University of Bologna
ClinicalTrials.gov Identifier: NCT00799799     History of Changes
Other Study ID Numbers: NK TRIAL
Study First Received: November 28, 2008
Last Updated: September 23, 2009
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on September 18, 2014