Safety and feasibility study of allogeneic ex vivo expanded NK cell therapy against advanced refractory/relapsed AML
Design
Conditioning regimens, including cyclophosphamide at a dose of 20 mg/Kg every day during 2-1 days before injection and fludarabine at a dose of 20 mg/ml every day due to 4-1 days before injection (for three days) would be prescribed to the patient.
One day after the completion of the conditioning regimen, 1-5 ×10^6 NK cells/Kg from an allogeneic source which have prepared in the laboratory would be injected due to 1 hour.
The second infusion on the 7th day with increasing doses includes 5 -10 million cells per kilogram of body weight would be infused without a conditioning regimen.
Settings and conduct
Receive conditioning regime, intravenous injection of Natural killer cells twice a week apart in hospitals with special cell therapy and transplantation awards
Participants/Inclusion and exclusion criteria
Inclusion Criteria:
Drug-resistant AML patients who have not responded to 2 treatment cycles or recurrent cases who are not candidates for routine therapies or bone marrow transplants. The toxicity or side effects of chemotherapy regimens such as severe cytopenia would be assigned and in case of severe symptoms, patients should be excluded from the study.
Exclusion Criteria
1- Simultaneously receiving chemotherapy drugs
2- CHF history during the last 6 months (Congestive Heart Failure)
3- USA history during the last 6 months (Unstable Angina)
4 - Active bacterial, fungal, or viral infections in the last month who have reduced the patient's tolerance to a new treatment
Intervention groups
Patient with Drug-resistant acute myeloid leukemia who will receive two dosage NK cells ( 1-5x10^6 per kg) after conditioning regimen receiving.
Main outcome variables
-No systemic toxicity and allergy reactions in the patients after cell injection
-reduction of tumor burden
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20200621047859N3
Registration date:2020-12-30, 1399/10/10
Registration timing:registered_while_recruiting
Last update:2020-12-30, 1399/10/10
Update count:0
Registration date
2020-12-30, 1399/10/10
Registrant information
Name
Ramin Sarrami Forooshani
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 8879 6003
Email address
rsf1351@gmail.com
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2020-09-22, 1399/07/01
Expected recruitment end date
2021-12-22, 1400/10/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Phase I/II Clinical Trial (Safety and feasibility) using ex-vivo expanded Haploidentical donor-derived (Natural Killer Cell)-NK Cells against advanced refractory/relapsed Acute Myeloid Leukemia (AML)
Public title
The Acute Myeloid Leukemia (AML) immune cell therapy using allogeneic ex-vivo expanded Natural Killer Cells (NK cells) transplantation
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
1- Age 18 to 70 years
2. Drug-resistant AML patients with no response to 2 treatments line or recurrent cases that can not be candidates for standard therapies or bone marrow transplants
3- The toxicity of chemotherapy regimens ( such as severe cytopenia) should be assigned and it would be checked as a regimen with no significant side effects.
4- PS≥2[Performance Status (PS)]
5- The results of these tests should be available:• [glomerular filtration rate (GFR)] GFR≥60 or CR≥2 mg / dl• ALT <2.5XULN / Bid≤2• O2Sat> 92% in room air• Cardiac classification status (III> NHC) or [ejection fraction]EF> 50%• Negative pregnancy test• Negative HIV testing
Exclusion criteria:
Age
From 18 years old to 70 years old
Gender
Both
Phase
1-2
Groups that have been masked
No information
Sample size
Target sample size:
30
Randomization (investigator's opinion)
Not randomized
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
Research Ethics Committee of Motamed Cancer Institute academic center for education, culture and res
Street address
No146, South Ghandi, Vanaq Square
City
Tehran
Province
Tehran
Postal code
1517964311
Approval date
2019-10-16, 1398/07/24
Ethics committee reference number
IR.ACECR.IBCRC.REC.1398.015
Health conditions studied
1
Description of health condition studied
Acute Myeloid Leukemia (AML)
ICD-10 code
C92.0
ICD-10 code description
Acute myeloblastic leukemia
Primary outcomes
1
Description
Possible symptoms of hyper-sensitivity and allergy after injection
Timepoint
Daily until the third day after the injection and then weekly until the day +90 after the injection
Method of measurement
Using CTCAE check list
2
Description
Decrease of tumor burden
Timepoint
A week after injection and every month until 3 months
Method of measurement
Physical Examination, Flow cytometry, CBC
3
Description
Graft versus host disease (GVHD) symptoms
Timepoint
Daily until the third day after the injection and then weekly until the day +90 after the injection
Method of measurement
Physical examination - Imaging - Laboratory tests
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group: Patients with acute resistant myeloid leukemia who receive conditioning regimen 3 days before cell therapy then 5-10 million cell per kilogram of patient weight would be infused intravenously one week apart
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
Imam Reza Hospital
Full name of responsible person
Dr Mohsen Rajaei nejhad
Street address
West Fatemi avenue, Etemadzade street
City
Tehran
Province
Tehran
Postal code
14117 1854
Phone
+98 21 8609 6931
Email
mrajaei@gmail.com
2
Recruitment center
Name of recruitment center
Shariati hospital
Full name of responsible person
Dr Maryam Barkhordari
Street address
North Kargar St., Jalal Al-Ahmad Intersection, Shariati Hospital
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 1000
Email
barkhordarm.n@gmail.com
3
Recruitment center
Name of recruitment center
Dei Hospital
Full name of responsible person
Dr Ardeshir Ghavamzadeh
Street address
Valiasr St., corner of Shahid Abbaspour
City
Tehran
Province
Tehran
Postal code
1517964311
Phone
+98 21 8879 7111
Email
ghavamza@sina.tums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Motamed Cancer Institute
Full name of responsible person
Dr Keivan Majidzadeh Ardebili
Street address
No146, South Ghandi, Vanaq Square
City
Tehran
Province
Tehran
Postal code
1517964311
Phone
+98 21 8879 6003
Email
K1majidzadeh@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
No
Title of funding source
Cell therapy budget of the Islamic Consultative Assembly
Proportion provided by this source
10
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other
2
Sponsor
Name of organization / entity
Modiriat Atiye Bahman Company
Full name of responsible person
Sina Hasnalizadeh
Street address
No-1, Ghasemi, Tabatabaei
City
Tehran
Province
Tehran
Postal code
1459973114
Phone
+98 21 8879 6003
Email
rsf1351@gmail.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Modiriat Atiye Bahman Company
Proportion provided by this source
90
Public or private sector
Private
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Other
Person responsible for general inquiries
Contact
Name of organization / entity
Iranian academic center for education culture and research
Full name of responsible person
Dr Ramin Sarrami Forooshani
Position
Associated Professor
Latest degree
Ph.D.
Other areas of specialty/work
Virology
Street address
No 146, South Ghandi, Vanaq Square
City
Tehran
Province
Tehran
Postal code
1517964311
Phone
+98 21 8879 6003
Email
rsf1351@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Iranian academic center for education culture and research
Full name of responsible person
Dr Ardeshir Ghavamzadeh
Position
Professor
Latest degree
Subspecialist
Other areas of specialty/work
Hematology-Oncology
Street address
No146, South Ghandi, Vanaq Square
City
Tehran
Province
Tehran
Postal code
1517964311
Phone
+98 21 8879 6003
Email
ghavamza@sina.tums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Iranian academic center for education culture and research
Full name of responsible person
Dr Zahra sadat Hashemi
Position
PhD
Latest degree
Ph.D.
Other areas of specialty/work
Medical Biotechnology
Street address
No146, Vanaq Square, South Ghandi
City
Tehran
Province
Tehran
Postal code
15179643111
Phone
+98 21 8879 6003
Email
z.hashemi87@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Not applicable
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available