Back to resultsNK Cell Infusion for Patients With Acute Myeloid Leukemia
Primary Purpose
Acute Myeloid Leukemia
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
chemotherapy combined with NK cells infusion
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
- AML patients receiving standard NCCN induction and consolidation chemotherapy;
- Age> = 18 years old;
- Relapsed and refractory AML: continued non-remission after induction and consolidation chemotherapy with NCCN standard protocol, or relapse after remission, or continued MRD positive;
- MDS-RAEB, MDS-AML, MPD-AML;
- ECOG≤3;
No serious organ dysfunction within 2 weeks before treatment:
- Heart: no arrhythmia and LVEF≥50% and no pericardial effusion;
- Liver: liver function <2 times the upper limit of ALT and <1.5 times the upper limit of total bilirubin, no active hepatitis;
- Kidney: serum creatinine <1.5 mg / dl; or if serum creatinine exceeds the upper limit, serum creatinine clearance should be CrCl> 50 ml / min;
- indoor fingertip blood oxygen saturation ≧ 92%;
- Expected survival time ≥ 3 months;
- The interval between re-induction therapy and NK cell therapy is at least 2 weeks, and the toxic and side effects of all induction remission treatments have disappeared; if the patient is receiving non-invasive chemotherapy, such as hydroxyurea, low-dose cytarabine, before receiving this program Should be discontinued before;
- All patients and donors are willing to join this clinical trial and sign informed consent.
Exclusion Criteria:
- Combined with a history of other malignant tumors <5 years (except cured skin basal cell carcinoma, cured cervical carcinoma in situ and gastrointestinal tumors confirmed to be cured by endoscopic mucosal resection);
- Have received bone marrow or organ transplant;
- Those who are allergic to the biological agents used in this treatment;
- active infection;
- Those who received other cell treatments such as DLI, CMV-CTL, EBV-CTL;
- HBV carriers;
- Patients with extramedullary recurrence;
- Chest radiographic examination to determine patients with pulmonary inflammation;
- Researchers do not consider it appropriate to participate in this trial.
Sites / Locations
- Peking University Institute of Hematology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AML patients with NK cells infusion
Arm Description
The relapsed/refractory AML patient received Flu+CTX (Flu 25mg/m2 (-6d to -2d)，CTX 1.0g/m2 (-6d to -5d) and haploidentical NK cells infusion postchemotherapy for at least 48 hours. NK cell dose was over 1+E07/ kg with 3 consecutive infusions. NK cells infusion interval was 1 day.
Outcomes
Primary Outcome Measures
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Closely monitor the patient's temperature, rash, BP, and other adverse reactions during the 48 hours after the infusion, and pay attention to acute and chronic GVHD; follow up once every 1-2 weeks within 6 months after the infusion, and review the blood count and biochemistry. Increase or decrease the relevant inspections and inspection frequencies as appropriate according to the condition;
Secondary Outcome Measures
Number of participants acheived CR post NK treatment
To evaluate the CR rate 1 month after NK treatment
Monitor the metabolism, migration and reconstruction of NK cells in vivo post NK treatment
The number of NK cells were evaluated before and after the completion of the infusion.
Assess the cell count recovery time of peripheral blood in chemotherapy combined with NK infusion
The blood count were evaluated closely before and after the completion of the infusion.
Number of participants relapsed post NK treatment
To evaluate the bone marrow status every months after NK treatment
Full Information
NCT ID
NCT04221971
First Posted
December 2, 2019
Last Updated
September 30, 2020
Sponsor
Peking University People's Hospital
Collaborators
The University of Science and Technology of China
1. Study Identification
Unique Protocol Identification Number
NCT04221971
Brief Title
NK Cell Infusion for Patients With Acute Myeloid Leukemia
Official Title
Clinical Study of Natural Killer Cell Infusion in Patients With Acute Myeloid Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Unknown status
Study Start Date
October 2020 (Anticipated)
Primary Completion Date
April 2021 (Anticipated)
Study Completion Date
April 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University People's Hospital
Collaborators
The University of Science and Technology of China
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Natural killer (NK) cells exert antitumor effects via their cytotoxic and cytokine-secreting capacity without present of clinical symptoms. In recent years, with the continuous advancement of in vitro expansion methods, the application of good quality management technology, NK cells could be clinical grade expanded without the need for pre-purification, feeder-free, and serum-free culture. In this clinical trial the investigators want to demonstrate the safety and efficacy chemotherapy combined with donor-derived in vitro activated NK cells infusion for high risk AML patients.
Detailed Description
Despite improvements in new drugs and allogeneic stem cell transplantation (allo-SCT), relapse remains a problem for patients with acute myeloid leukemia (AML). Natural killer (NK) cells exert antitumor effects via their cytotoxic and cytokine-secreting capacity without present of clinical symptoms.
In recent years, with the continuous advancement of in vitro expansion methods, the application of good quality management technology (GMP technology), NK cells could be clinical grade expanded without the need for pre-purification, feeder-free, and serum-free culture. Preclinical studies have confirmed that adoptive infusion expanded and activated NK cells can specifically recognize and kill tumor cells in mice without causing GVHD, which is a safe and effective treatment.
Therefore, in this clinical trial the investigators want to enroll patients with acute AML (excluding APL) who are continued to be unresolved, or relapsed after remission, or continued to be MRD-positive after induction and consolidation according to NCCN standard chemotherapy regimen. Chemotherapy was combined with donor-derived in vitro activated NK cells infusion to evaluate the safety and effectiveness effect of NK cells and to explore the dynamics of NK in vivo after adoptive infusion.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AML patients with NK cells infusion
Arm Type
Experimental
Arm Description
The relapsed/refractory AML patient received Flu+CTX (Flu 25mg/m2 (-6d to -2d)，CTX 1.0g/m2 (-6d to -5d) and haploidentical NK cells infusion postchemotherapy for at least 48 hours. NK cell dose was over 1+E07/ kg with 3 consecutive infusions. NK cells infusion interval was 1 day.
Intervention Type
Drug
Intervention Name(s)
chemotherapy combined with NK cells infusion
Other Intervention Name(s)
cyclophosphamide (Cy, 1000 mg/m2/day, day -6 to -5), and fludarabine (Flu, 25 mg/m2/day, day -6 to -2)
Intervention Description
chemotherapy combined with NK cells infusion
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Description
Closely monitor the patient's temperature, rash, BP, and other adverse reactions during the 48 hours after the infusion, and pay attention to acute and chronic GVHD; follow up once every 1-2 weeks within 6 months after the infusion, and review the blood count and biochemistry. Increase or decrease the relevant inspections and inspection frequencies as appropriate according to the condition;
Time Frame
Two months after NK treatment
Secondary Outcome Measure Information:
Title
Number of participants acheived CR post NK treatment
Description
To evaluate the CR rate 1 month after NK treatment
Time Frame
One month after NK treatment
Title
Monitor the metabolism, migration and reconstruction of NK cells in vivo post NK treatment
Description
The number of NK cells were evaluated before and after the completion of the infusion.
Time Frame
One month after NK treatment
Title
Assess the cell count recovery time of peripheral blood in chemotherapy combined with NK infusion
Description
The blood count were evaluated closely before and after the completion of the infusion.
Time Frame
Two months after NK treatment
Title
Number of participants relapsed post NK treatment
Description
To evaluate the bone marrow status every months after NK treatment
Time Frame
Every months after NK treatment within 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
AML patients receiving standard NCCN induction and consolidation chemotherapy;
Age> = 18 years old;
Relapsed and refractory AML: continued non-remission after induction and consolidation chemotherapy with NCCN standard protocol, or relapse after remission, or continued MRD positive;
MDS-RAEB, MDS-AML, MPD-AML;
ECOG≤3;
No serious organ dysfunction within 2 weeks before treatment:
Heart: no arrhythmia and LVEF≥50% and no pericardial effusion;
Liver: liver function <2 times the upper limit of ALT and <1.5 times the upper limit of total bilirubin, no active hepatitis;
Kidney: serum creatinine <1.5 mg / dl; or if serum creatinine exceeds the upper limit, serum creatinine clearance should be CrCl> 50 ml / min;
indoor fingertip blood oxygen saturation ≧ 92%;
Expected survival time ≥ 3 months;
The interval between re-induction therapy and NK cell therapy is at least 2 weeks, and the toxic and side effects of all induction remission treatments have disappeared; if the patient is receiving non-invasive chemotherapy, such as hydroxyurea, low-dose cytarabine, before receiving this program Should be discontinued before;
All patients and donors are willing to join this clinical trial and sign informed consent.
Exclusion Criteria:
Combined with a history of other malignant tumors <5 years (except cured skin basal cell carcinoma, cured cervical carcinoma in situ and gastrointestinal tumors confirmed to be cured by endoscopic mucosal resection);
Have received bone marrow or organ transplant;
Those who are allergic to the biological agents used in this treatment;
active infection;
Those who received other cell treatments such as DLI, CMV-CTL, EBV-CTL;
HBV carriers;
Patients with extramedullary recurrence;
Chest radiographic examination to determine patients with pulmonary inflammation;
Researchers do not consider it appropriate to participate in this trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiang-Yu Zhao, M.D.
Phone
8610-88325949
Email
zhao_xy@bjmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiao-Jun Huang, M.D.
Organizational Affiliation
Peking University People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking University Institute of Hematology
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100044
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
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NK Cell Infusion for Patients With Acute Myeloid Leukemia
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