Feasibility, safety, effectiveness and toxicity of Post-transplant Expanded, Activated Haploidentical Natural Killer Cells Infusion in Haploidentical Hematopoietic Stem Cell Transplantation for Pediatric Patients with Acute Myeloid Leukemia: A Pilot Study
Infusion of expanded NK cells from healthy haploidentical donors to enhance anti -eukemia effect in pediatric patients with acute myeloid leukemia.
Design
A Pilot single arm clinical trial of 5 Patients
Settings and conduct
1. Haploidentical donors will donate 30 cc/kg (recipient body weight) of blood collected on day −30 for NK-cell production and will undergo peripheral blood apheresis on day 0 of transplant.
2. NK cells will be expanded and activated.
3. The purity of the product would be checked by flowcytometery using NK cell markers.
4. Assesment of activation of NK-cell product would be conducted via evaluation of cytokine secretion including IFN-γ.
5. Assesment of the product viability would be conducted via trypan blue dye exclusion.
6. Assesment of the functionality of the product would be done via cytotoxicity assay.
7. NK-cell product will be infused from cryopreserved aliquots on days +5 post transplant .
Participants/Inclusion and exclusion criteria
1. Age ≤ 18 years old.
2. Diagnosis of AML other than acute promyelocytic leukemia (APL) / candidate for first allogenic haploidentical HSCT.
3. Adequate organ function
4. Karnofsky or Lansky performance score of greater than or equal to 50.
5. At least two weeks since receipt of any systemic chemotherapy and/or radiation therapy.
Intervention groups
In this single arm study, Haploidentical activated expanded NK cell will be infused after Haploidentical HSCT in pediatric patients with AML.
Main outcome variables
1. To evaluate 1 year overall survival after infusion of expanded haploidentical NK cells.
2. To evaluate 1 year relapse-free survival after infusion of expanded haploidentical NK cells.
3. To evaluate 1 year relapse rate after infusion of expanded haploidentical NK cells.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20140818018842N33
Registration date:2023-04-03, 1402/01/14
Registration timing:registered_while_recruiting
Last update:2023-04-03, 1402/01/14
Update count:0
Registration date
2023-04-03, 1402/01/14
Registrant information
Name
Leyla Sharifi Aliabadi
Name of organization / entity
Research Institute for Hematology, Oncology and Stem Cell Transplantation,Tehran University of Medic
Country
Iran (Islamic Republic of)
Phone
+98 21 8490 3691
Email address
ctu@sina.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-03-21, 1402/01/01
Expected recruitment end date
2025-03-21, 1404/01/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Feasibility, safety, effectiveness and toxicity of Post-transplant Expanded, Activated Haploidentical Natural Killer Cells Infusion in Haploidentical Hematopoietic Stem Cell Transplantation for Pediatric Patients with Acute Myeloid Leukemia: A Pilot Study
Public title
Feasibility, safety, effectiveness and toxicity of Post-transplant Expanded, Activated Haploidentical Natural Killer Cells Infusion in Haploidentical Hematopoietic Stem Cell Transplantation for Pediatric Patients with Acute Myeloid Leukemia: A Pilot Study
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Age ≤ 18 years old.
Patients must have a diagnosis of AML other than acute promyelocytic leukemia (APL) according to WHO criteria and should be a candidate for their first allogenic haploidentical HSCT.
All patients must have adequate organ function defined as:a. Renal Function: Age-adjusted serum creatinine ≤ to 1.5 x normal for age/gender OR creatinine clearance or GFR greater than or equal to 60 cc/min/1.73m2b. Liver Function: Total bilirubin ≤ 1.5 x normal for age, AND Alanine aminotransferase (ALT) is no more than 2 times the upper limit of normal and Aspartate transaminases (AST) is no more than 2 times the upper limit of normal.c. Cardiac Function: Normal ejection fraction documented by either echocardiogram or radionuclide MUGA evaluation OR Normal fractional shortening documented by echocardiogramd. Pulmonary Function: No dyspnea at rest, no oxygen requirement.
Karnofsky or Lansky performance score of greater than or equal to 50.
Potentially available haploidentical family donor (child/ sibling), willing and fit for NK cell donation
At least two weeks since receipt of any biological therapy, systemic chemotherapy, and/or radiation therapy.
Exclusion criteria:
Pregnancy: Quantitative Serum B-HCG must be negative in girls who are post-menarchal
Breast feeding women are not eligible.
Active or uncontrolled infection
Patient declines participation
Second HSC
Age
To 18 years old
Gender
Both
Phase
1-2
Groups that have been masked
No information
Sample size
Target sample size:
5
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
Tehran University of Medical Sciences
Street address
North kargar st
City
Tehran
Province
Tehran
Postal code
146767
Approval date
2022-10-10, 1401/07/18
Ethics committee reference number
IR.TUMS.MEDICINE.REC.1401.540
Health conditions studied
1
Description of health condition studied
Acute Myeloid Leukemia
ICD-10 code
C92.0
ICD-10 code description
Acute myeloid leukemia
Primary outcomes
1
Description
Relapse free survival
Timepoint
1 year
Method of measurement
spss
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group: Pediatric Patients with Acute Myeloid Leukemia who are candidate to recieve Haploidentical Hematopoietic Stem Cell Transplantation 1. Haploidentical donors will donate 30 cc/kg (recipient body weight) of blood collected on day −30 for NK-cell production and will undergo peripheral blood apheresis on day 0 of transplant.2. NK cells will be expanded and activated.3. The purity of the product would be checked by flowcytometery using NK cell markers.4. Assesment of activation of NK-cell product would be conducted via evaluation of cytokine secretion including IFN-γ.5. Assesment of the product viability would be conducted via trypan blue dye exclusion.6. Assesment of the functionality of the product would be done via cytotoxicity assay.7. NK-cell product will be infused from cryopreserved aliquots on days +5 post transplant .
Category
Treatment - Other
Recruitment centers
1
Recruitment center
Name of recruitment center
Research Institute for Oncology, Hematology and Cell TherapyHematology
Full name of responsible person
Tahereh Rostami
Street address
North kargar st
City
Tehran
Province
Tehran
Postal code
146767
Phone
+98 912 389 0394
Email
trostami@sina.tums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Marjan Yaghmaie
Street address
North kargar st
City
Tehran
Province
Tehran
Postal code
146767
Phone
+98 912 389 0394
Email
m-yaghmaie@sina.tums.ac.ir
Web page address
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
100
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
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Azadeh Kiumarsi
Position
Assistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Hematology
Street address
North kargar st
City
Tehran
Province
Tehran
Postal code
146767
Phone
+98 912 389 0394
Email
akiumarsi@sina.tums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Tahereh Rostami
Position
Assistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Hematology
Street address
North kargar st
City
Tehran
Province
Tehran
Postal code
146767
Phone
+98 912 389 0394
Email
trostami@sina.tums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Azadeh Kiumarsi
Position
Assistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Hematology
Street address
North kargar st
City
Tehran
Province
Tehran
Postal code
146767
Phone
+98 912 103 7104
Fax
+98 21 8800 4140
Email
akiumarsi@sina.tums.ac.ir
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
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
No - There is not a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available