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

NCT ID: NCT03955848

Last Updated: 2021-01-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-11
• Study Completion Date: 2022-05-11

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.

Conditions

Adult Acute Myeloid Leukemia in Remission

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ARM 1

NK cell infusion

Group Type: EXPERIMENTAL

Alloreactive NK cell infusion

Intervention Type: BIOLOGICAL

Alloreactive NK cell infusion

ARM 2

Follow up without treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Alloreactive NK cell infusion

Alloreactive NK cell infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

Alloreactive NK cells

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)

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS Azienda Ospedaliero-Universitaria di Bologna

OTHER

Sponsor Role: lead

Responsible Party

Antonio Curti

Medical Doctor, Hematologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Antonio Curti

Role: PRINCIPAL_INVESTIGATOR

Istituto di Ematologia Seràgnoli, Ospedale S.Orsola-Malpighi, Bologna

Locations

Antonio Curti

Bologna, BO, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Antonio Curti

Role: CONTACT

antonio.curti2@unibo.it

+390512144074

Facility Contacts

Antonio Curti

Role: primary

antonio.curti2@unibo.it

+390512144074

Other Identifiers

35/2017/O/Sper

Identifier Type: -

Identifier Source: org_study_id