Investigating the safety and efficacy of active natural killer cell infusions in patients with MRD-positive Acute Lymphoblastic Leukemia after hematopoietic stem cell transplantation: a phase I/II trial
To assess the safety and efficacy of administration of Natural Killer cells in patients with MRD-positive Acute Lymphoblastic Leukemia early after hematopoietic stem cell transplantation.
Design
This is a non-randomized, interventional, single-group assignment study to assess the safety and efficacy of allogeneic NK cell therapy on 36 patients with MRD-positive Acute Lymphoblastic Leukemia who are candidates for allogeneic hematopoietic stem cell transplantation.
Settings and conduct
The study is a single-group clinical trial to evaluate the safety and efficacy of Prophylactic administration of Natural Killer cells early after hematopoietic stem cell transplantation in adult patients with MRD-positive Acute Lymphoblastic Leukemia at the Hematology-Oncology-Stem Cell Transplantation Research Center (HORCSCT) of Tehran University.
Participants/Inclusion and exclusion criteria
Patients over and equal to 18 years of age with MRD-positive Acute Lymphoblastic Leukemia who are candidates for allogeneic hematopoietic stem cell transplantation from matched or mismatched donors are included in the study. Patients with uncontrolled infection or severe acute graft-versus-host disease are excluded from the study.
Intervention groups
All patients will be assigned to the only interventional arm of the study. Recipients of allogeneic Stem Cell Transplantation will receive the systemic intravenous infusion of natural killer cells at days +6 and +12 post-transplantation.
Main outcome variables
Natural Killer cell infusion-related Adverse Events, Relapse incidence for one year after infusion.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20140818018842N38
Registration date:2024-05-07, 1403/02/18
Registration timing:prospective
Last update:2024-05-07, 1403/02/18
Update count:0
Registration date
2024-05-07, 1403/02/18
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 2635
Email address
ctu@sina.tums.ac.ir
Recruitment status
recruiting
Funding source
Expected recruitment start date
2024-05-09, 1403/02/20
Expected recruitment end date
2025-06-10, 1404/03/20
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Investigating the safety and efficacy of active natural killer cell infusions in patients with MRD-positive Acute Lymphoblastic Leukemia after hematopoietic stem cell transplantation: a phase I/II trial
Public title
Natural Killer cell in Acute Lymphoblastic Leukemia
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Age 18 years old or more
Patients with B-ALL or T-ALL who are MRD positive after receiving therapy.
Exclusion criteria:
Symptomatic coronary artery disease
Karnofsky Performance Score < 60
Patients with uncontrolled bacterial, viral or fungal infection
Acute graft versus host disease
Females who are pregnant or breastfeeding.
Age
From 18 years old to 65 years old
Gender
Both
Phase
1-2
Groups that have been masked
No information
Sample size
Target sample size:
36
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
Ethic committee of Hematology- Oncology and Stem Cell Transplantation Research Center, Tehran Univer
Street address
Kargar shomali Ave., Shariati hospital
City
Tehran
Province
Tehran
Postal code
1411713131
Approval date
2022-10-23, 1401/08/01
Ethics committee reference number
IR.TUMS.HORCSCT.REC.1401.039
Health conditions studied
1
Description of health condition studied
acute lymphoblastic leukemia
ICD-10 code
C91.0
ICD-10 code description
Acute lymphoblastic leukemia [ALL]
Primary outcomes
1
Description
Number of Patients With Grades 3-5 of Natural Killer cell infusion-related Adverse Events.
Timepoint
Daily during the first seven days after the injection
Method of measurement
History, Physical exam, and lab test
2
Description
Relapse Incidence
Timepoint
one year after infusion
Method of measurement
Bone marrow aspiration and biopsy
Secondary outcomes
1
Description
Determination of MRD negativity in patients after injection of natural killer cells
Timepoint
1, 3, 6, 9 and 12 months post transplant
Method of measurement
Bone marrow aspiration and flowcytometry
2
Description
Incidence of acute graft versus host disease
Timepoint
Monthly for 4 months after transplantation
Method of measurement
Visiting the patient in person and performing monthly lab tests in outpatient clinique
Intervention groups
1
Description
Intervention group: All patients are included in the only intervention arm of the study. Patients in the intervention arm will receive two doses of in-vitro expanded NK cells at the 6 and 12 days after transplantation under full supervision and in an isolated room. The process of isolation and preparation of NK cells will be done in a clean room with clinical grade and suitable conditions for producing NK cells. 20 to 30 cc of peripheral blood was taken from the third-party donor and after the isolation of mononuclear cells, CD56+/CD3- reproduced. A viability test is done using trypan blue and phenotyping is used to check the absolute number and purity of cells.
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Hematology- Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sci
Full name of responsible person
Tanaz Sayar Bahri
Street address
North Kargar Ave.
City
Tehran
Province
Tehran
Postal code
1417713135
Phone
+98 21 8800 4140
Email
tanaz.bahri@gmail.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr. Ali Akbari Sari
Street address
Poursina St., 16 Azar St., Keshavarz Blvd.
City
Tehran
Province
Tehran
Postal code
1416634793
Phone
+98 21 81631
Email
akbarisari@tums.ac.ir
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
Maryam Barkhordar
Position
Assistant professor
Latest degree
Subspecialist
Other areas of specialty/work
Hematology
Street address
Kargar-e-Shomali Ave.
City
Tehran
Province
Tehran
Postal code
1411713131
Phone
+98 21 8800 4140
Email
barkhordarm.n@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Mohamad ٰVaezi
Position
Associate Professor
Latest degree
Subspecialist
Other areas of specialty/work
Hematology
Street address
Kargar-e-Shomali Ave.
City
Tehran
Province
Tehran
Postal code
1411713131
Phone
+98 21 8800 4140
Email
vaezi.mohammad@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Tanaz Sayar Bahri
Position
Assistant Professor
Latest degree
Subspecialist
Other areas of specialty/work
Hematology
Street address
Kargar-e-Shomali Ave.
City
Tehran
Province
Tehran
Postal code
1411713131
Phone
+98 21 8800 4140
Email
tanaz.bahri@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
No - There is not a plan to make this available
Justification/reason for indecision/not sharing IPD
Justification/reason for indecision/not sharing IPD