Clinical trial NCT03955848: INFUSION OF ALLOREACTIVE NATURAL KILLER (NK) CELLS AS CONSOLIDATION STRATEGY FOR ACUTE MYELOID LEUKEMIA PATIENTS
Official title: INFUSION OF ALLOREACTIVE NK CELLS AS CONSOLIDATION STRATEGY FOR ADULT ACUTE MYELOID LEUKEMIA PATIENTS: A MULTICENTER CLINICAL STUDY
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Adult Acute Myeloid Leukemia in Remission
Keywords: AML in Remission
NK cells
Immunotherapy
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
First posted: 2019-05-20
Enrollment: 80
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: relapse free survival
timeFrame: 36 months
measure: overall survival
timeFrame: 36 months
Secondary outcomes:
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Antonio Curti
state: BO
Study officials:
affiliation: Istituto di Ematologia Seràgnoli, Ospedale S.Orsola-Malpighi, Bologna
name: Antonio Curti
role: PRINCIPAL_INVESTIGATOR
References: