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出境医 / 临床实验 / INFUSION OF ALLOREACTIVE NATURAL KILLER (NK) CELLS AS CONSOLIDATION STRATEGY FOR ACUTE MYELOID LEUKEMIA PATIENTS (NKAML)

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

Study Description
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.

Condition or disease Intervention/treatment Phase
Adult Acute Myeloid Leukemia in Remission Biological: Alloreactive NK cell infusion Not Applicable

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: INFUSION OF ALLOREACTIVE NK CELLS AS CONSOLIDATION STRATEGY FOR ADULT ACUTE MYELOID LEUKEMIA PATIENTS: A MULTICENTER CLINICAL STUDY
Actual Study Start Date : May 11, 2018
Actual Primary Completion Date : May 16, 2019
Estimated Study Completion Date : May 11, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: ARM 1
NK cell infusion
 Biological: Alloreactive NK cell infusion
Alloreactive NK cell infusion
Other Name: Alloreactive NK cells
No Intervention: ARM 2
Follow up without treatment
Outcome Measures
Primary Outcome Measures :
  1. relapse free survival [ Time Frame: 36 months ]
    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.

  2. overall survival [ Time Frame: 36 months ]
    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.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Antonio Curti +390512144074 antonio.curti2@unibo.it

Locations
Layout table for location information
Italy
Antonio Curti Recruiting
Bologna, BO, Italy, 40138
Contact: Antonio Curti    +390512144074    antonio.curti2@unibo.it   
Sponsors and Collaborators
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Investigators
Layout table for investigator information
Principal Investigator: Antonio Curti Istituto di Ematologia Seràgnoli, Ospedale S.Orsola-Malpighi, Bologna
Tracking Information
First Submitted Date  ICMJE April 12, 2019
First Posted Date  ICMJE May 20, 2019
Last Update Posted Date January 20, 2021
Actual Study Start Date  ICMJE May 11, 2018
Actual Primary Completion Date May 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 17, 2019)
  • relapse free survival [ Time Frame: 36 months ]
    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.
  • overall survival [ Time Frame: 36 months ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE INFUSION OF ALLOREACTIVE NATURAL KILLER (NK) CELLS AS CONSOLIDATION STRATEGY FOR ACUTE MYELOID LEUKEMIA PATIENTS
Official Title  ICMJE INFUSION OF ALLOREACTIVE NK CELLS AS CONSOLIDATION STRATEGY FOR ADULT ACUTE MYELOID LEUKEMIA PATIENTS: A MULTICENTER CLINICAL STUDY
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adult Acute Myeloid Leukemia in Remission
Intervention  ICMJE Biological: Alloreactive NK cell infusion
Alloreactive NK cell infusion
Other Name: Alloreactive NK cells
Study Arms  ICMJE
  • Experimental: ARM 1
    NK cell infusion
    Intervention: Biological: Alloreactive NK cell infusion
  • No Intervention: ARM 2
    Follow up without treatment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 17, 2019) 		80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 11, 2022
Actual Primary Completion Date May 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Antonio Curti +390512144074 antonio.curti2@unibo.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03955848
Other Study ID Numbers  ICMJE 35/2017/O/Sper
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Antonio Curti, IRCCS Azienda Ospedaliero-Universitaria di Bologna
Study Sponsor  ICMJE IRCCS Azienda Ospedaliero-Universitaria di Bologna
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Antonio Curti Istituto di Ematologia Seràgnoli, Ospedale S.Orsola-Malpighi, Bologna
PRS Account IRCCS Azienda Ospedaliero-Universitaria di Bologna
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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