1. Safety evaluation (tolerability of adverse effects) of intravenous injection of allogeneic natural killer cells to adult patients with relapsed/refractory acute myeloid leukemia
2. Evaluating the effectiveness of treatment (induction of GVL effect) of allogeneic natural killer cells in adult patients with relapsed/refractory acute myeloid leukemia.
Design
Phase 2 clinical trial without control group on 5 patients
Settings and conduct
The preparation and injection of the first round of NK is done as soon as entering the study. Injections are done in three times, once a week. Before receiving NK cells, fludarabine and cyclophosphamide are prescribed. NK suspended in 50 ml of 5% albumin solution is injected intravenously (central vein) for 15-20 minutes. In each NK injection, the number of injected live cells is determined based on the patient's weight. The injected NK cell is considered to be at least 106 cells per kilogram of body weight.
Participants/Inclusion and exclusion criteria
Inclusion criteria: 1- Patients with AML of both genders in the age range of 18 to 65 years
2- Patients with known involvement of CNS with AML provided that they have been treated and CSF is clear for at least 2 weeks before enrollment in the study.
3- ECOG functional status less than or equal to 2.
4- Adequate functioning of organs
5- Be able to stop using corticosteroids and other immunosuppressive drugs from the 3rd day of the trial and up to 30 days after the injection of NK cells.
6- Absence of pregnancy or breastfeeding
7- Failure to receive any research drug within 14 days before the start of the clinical trial
8- The ability to understand and the willingness to sign a certified informed consent document (or if there is an authorized legal representative)
Intervention groups
Transfusion of allogenic natural killer cells
Main outcome variables
NK cell; GvHD grade III; ST2; REG3α; S100; TIM3; HGF
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20200417047113N2
Registration date:2023-01-25, 1401/11/05
Registration timing:registered_while_recruiting
Last update:2023-01-25, 1401/11/05
Update count:0
Registration date
2023-01-25, 1401/11/05
Registrant information
Name
Sahar Shojaei
Name of organization / entity
Middle East Gene Therapy project
Country
Iran (Islamic Republic of)
Phone
+98 21 4478 7327
Email address
shojaeisahar@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2022-12-22, 1401/10/01
Expected recruitment end date
2024-12-21, 1403/10/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of efficacy and safety of allogeneic activated Natural Killer cells in adult patients with relapsed/refractory acute myeloid leukemia.
Public title
Effect of treatmen with natural killer cells in acute myeloid leukemia
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Patients with AML of both genders in the age range of 18 to 65 years with the following conditions:• Refractory AML that has not fully recovered after induction therapy.• Relapsed AML that is not a candidate for bone marrow allogeneic transplantation.• High-risk AML (based on ELN criteria) in complete remission (CR) but currently not a candidate for allogeneic bone marrow transplantation.• Relapsed AML after bone marrow transplantation
Patients with known CNS involvement with AML provided that they had been treated and the CSF was clear for at least 2 weeks prior to study enrollment
ECOG performance status less than or equal to 2
Adequate performance of organs as follows:• Total bilirubin ≤ 2 mg/dL• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN• Creatinine within normal institutional limits OR creatinine clearance ≥ 50 mL/min/1.73 m2 by Cockcroft-Gault Formula (adults) or Schwartz formula (pediatric cohort)• Oxygen saturation ≥90% on room air• Ejection fraction ≥50%
Be able to stop using corticosteroids and other immunosuppressive drugs from day 3- the beginning of the trial and up to 30 days after the injection of NK cells. However, if clinically necessary, the use of low-level corticosteroids is allowed. Low-level corticosteroid use was defined as 10 mg or less of prednisone (or equivalent for other steroids) per day
Not pregnant or breastfeeding
Failure to receive any research drug within 14 days before the start of the clinical trial
Ability to understand and willingness to sign a certified informed consent document (or if there is an authorized legal representative)
Exclusion criteria:
Uncontrolled bacterial or viral infections, or known HIV, hepatitis B or C infection
Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG indicating acute ischemia or active conduction system abnormalities
New progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that were not evaluated by bronchoscopy. Infiltrations attributed to infection should be stable and improving after 1 week of appropriate therapy (4 weeks for suspected or proven fungal infections)
Known sensitivity to one or more study agents
Active autoimmune disease that requires systemic immunosuppression treatment
Known history of other cancers in the last 5 years
Age
From 18 years old to 65 years old
Gender
Both
Phase
2
Groups that have been masked
No information
Sample size
Target sample size:
5
Randomization (investigator's opinion)
N/A
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Single
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Vice President of Research and Technology Shahid Beheshti University of Medical Sciences (Research E
Street address
Shahid Beheshti Medical university, Yaman St, Shahid Chamran Highway
City
Tehran
Province
Tehran
Postal code
1985717443
Approval date
2021-11-28, 1400/09/07
Ethics committee reference number
IR.SBMU.RETECH.REC.1400.671
Health conditions studied
1
Description of health condition studied
Acute Myeloid leukemia
ICD-10 code
C92.0
ICD-10 code description
Acute myeloblastic leukemia
Primary outcomes
1
Description
percentage of peripheral blood blast
Timepoint
Before treatment and then 4,8 and 12 weeks after treatment
Method of measurement
Peripheral blood Flowcytometry
2
Description
Hematologic parameters
Timepoint
before starting the treatment and then weekly until 6 weeks and then monthly
Method of measurement
CBC
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group: The preparation and injection of the first round of natural killer cells (NK) is done as soon as entering the study. Injections are done in three times, once a week. Before receiving NK cells, fludarabine and cyclophosphamide drugs are prescribed. NK suspended in 63 ml of 6% albumin solution is injected intravenously (central vein) for 16-23 minutes. In each NK injection, the number of injected live cells is determined based on the patient's weight. The injected NK cell is considered to be at least 10 to the power of 6 cells per kilogram of body weight. The number of injected cells is calculated based on the number of living cells.