INFUSION OF ALLOREACTIVE NATURAL KILLER (NK) CELLS AS CONSOLIDATION STRATEGY FOR ACUTE MYELOID LEUKEMIA PATIENTS (NKAML)

INFUSION OF ALLOREACTIVE NK CELLS AS CONSOLIDATION STRATEGY FOR ADULT ACUTE MYELOID LEUKEMIA PATIENTS: A MULTICENTER CLINICAL STUDY

Acute Myeloid Leukemia (AML) patients who had achieved Complete Remission (CR) after (re)induction/consolidation chemotherapy will receive the infusion of alloreactive NK cells. Adult AML patients in morphologic, but not cytogenetic and/or molecular CR and AML patients in morphologic plus cytogenetic and/or molecular CR, not eligible for Stem Cell Transplantation (SCT), will be included. Using a genetic randomization through a 'donor' vs 'no donor' approach, patients will undergo NK cell infusion (ARM 1) or followed-up without treatment (ARM 2). Donor alloreactive NK cell repertoire will be evaluated in order to determine the functional cell dose to be used for NK cell collection. NK cells will be selected from a steady-state large volume leukapheresis product from a suitable KIR-ligand incompatible donor. NK cell purification will be performed if the donor leukapheresis product contains at least 10x106 NK cells/Kg, otherwise the final decision for proceeding to NK purification will be made by the PI after careful evaluation of the number of alloreactive If the minimum collected cell dose of 2x105 total alloreactive NK cells/kg is not reached after a single leukapheresis, donors could undergo a second PB collection within 30 days from the first one. Patients will receive immunosuppressive chemotherapy, fludarabine (Flu) 25 mg/mq/ from day -7 to -3 and cyclophosphamide (Cy) 4 g/mq on day -2 (Flu/Cy). Immunosuppressive chemotherapy is not part of the procedures under study and it is used to favor NK cell engraftment. Two days after Cy administration, patients will be infused intravenously with a single dose of cryopreserved NK cells (day 0), which will be followed by subcutaneous administration of Interleuki (IL)-2 (10 x 106 IU/day, 3 times weekly) for 2 weeks (6 doses total). IL-2 administration is not part of the procedures under study and it is used to favor early in vivo expansion of infused NK cells. Peripheral blood samples will be collected for molecular assessment of microchimerism and tracking of NK cells for 30 days, immunophenotype studies, alloreactive NK cells cloning and functional assays. Bone marrow aspirate will be performed once a week until hematological recovery. Enrolled patients (ARM1 and 2) will be followed up for at least 12 months after NK cell infusion. RFS is defined as the time from patient enrollment to disease relapse.

Study Overview

• Status: Unknown
• Conditions: Adult Acute Myeloid Leukemia in Remission
• Intervention / Treatment: Biological: Alloreactive NK cell infusion

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • BO
    • Bologna, BO, Italy, 40138
      • Recruiting
      • Antonio Curti
      • Contact: Antonio Curti; Phone Number: +390512144074; Email: antonio.curti2@unibo.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent.

  • AML patients in morphologic, but not cytogenetic or molecular CR
  • AML patients in morphologic plus cytogenetic or molecular CR
• Performance Status ≥ 70% (Karnofsky score) or ≤ 2 (WHO)
• Age ≥ 18 years
• Adequate renal (serum creatinine < 2 mg/dl), pulmonary (Sat O2 ≥ 96%) and hepatic function.
• Left Ventricular Ejection Fraction (LVEF) of ≥ 50% as determined by - Echocardiogram

Exclusion Criteria:

• Eligibility to SCT
• Low-risk AML patients in molecular CR
• HIV positivity.
• Hepatiti C Virus positivity (serology and viremia)
• Pregnant or nursing females
• Current uncontrolled infection
• Signs or symptoms of fluid retention (e.g. pleural effusion)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ARM 1; NK cell infusion	Biological: Alloreactive NK cell infusion; Alloreactive NK cell infusion; Other Names: Alloreactive NK cells
NO_INTERVENTION: ARM 2; Follow up without treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
relapse free survival	relapse-free survival (RFS) of AML patients, not eligible for SCT, who undergo alloreactive NK cell infusion after the achievement of CR with induction/consolidation chemotherapy.	36 months
overall survival	overall survival (RFS) of AML patients, not eligible for SCT, who undergo alloreactive NK cell infusion after the achievement of CR with induction/consolidation chemotherapy.	36 months

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
• Investigators: Principal Investigator: Antonio Curti, Istituto di Ematologia Seràgnoli, Ospedale S.Orsola-Malpighi, Bologna

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 11, 2018
• Primary Completion (ACTUAL): May 16, 2019
• Study Completion (ANTICIPATED): May 11, 2022

Study Registration Dates

• First Submitted: April 12, 2019
• First Submitted That Met QC Criteria: May 17, 2019
• First Posted (ACTUAL): May 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 18, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Immunotherapy; NK cells; AML in Remission
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 35/2017/O/Sper

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No