Leukemia, Acute MyeloidPhase 1NCT04327037
Safety of Expanded Haploidentical Natural Killer Cells for Leukemia
A Phase 1 study testing Expanded Haploidentical Natural Killer cells and IL-2 in people with Leukemia, Acute Myeloid and Leukemia, Acute Lymphoblastic, run by Belarusian Research Center for Pediatric Oncology, Hematology and Immunology at 1 site in Belarus.
Trial summary
The purpose of this study is to estimate the safety of ex vivo expanded haploidentical natural killer (NK) cells for patients with leukemia. Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Leukemia, Acute Myeloid, Leukemia, Acute Lymphoblastic
- What is being tested?
- Expanded Haploidentical Natural Killer cells and IL-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteBelarus
- Study dates
- 2 Jan 2019to 30 Jun 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients:
- Relapsed acute myeloid or lymphoblastic leukemia
- Primary refractory myeloid or lymphoblastic leukemia
- Karnofsky or Lansky performance scale greater or equal to 70
- Written informed consent
- Donor:
Show all 10Show fewer
- Haploidentical family donor
- > 18 years old
- Donor suitable for cell donation and apheresis according to standard criteria
- Written informed consent
Who cannot join
- Patients:
- Uncontrolled infection
- Severe hepatic dysfunction: SGOT or SCPT >=5x upper limit of normal for age
- Positive serology for human immunodeficiency virus (HIV)
- Donors:
- Pregnancy or breast feeding
- Positive serology for HIV, hepatitis B or C.
Trial locations and contacts
1 site in 1 country.
Belarus1 site
Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
Minsk, Minsk Oblast, 223053
About this study
Official title: Pilot Study of Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Leukemia
The purpose of this study is to estimate the safety of ex vivo expanded haploidentical natural killer (NK) cells for patients with leukemia.
Read the detailed description
Immunotherapy with natural killer (NK) cells may improve the results of treatment for patients with cancer. However, for better efficiency high doses of NK cells are required. For this purpose, NK cells were expanded in the presence of feeder K562 cells gene-modified for expression 4-1BBL and membrane bound IL-21. In the result of expansion, large number of activated NK cells are obtained.
Protocol of immunotherapy includes conditioning (fludarabine + cyclophosphamide or any other protocol of chemotherapy) followed by expanded NK cells intravenous infusion. To sustain proliferation of donor NK cells in vivo patients receive 6 doses of Il-2 every second day. 10 patients will be enrolled in phase I to test different doses of NK cells: 20, 50, 70, 100 and >100 x 10^6/kg.
- Being tested
- Expanded Haploidentical Natural Killer cells, IL-2
- Keywords
- Immunotherapy, Natural killer cells
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Expanded Haploidentical Natural Killer cellsBiological
One dose (from 20x to >100x 10^6 /kg) of expanded haploidentical NK cells
IL-2Drug
Also called Ronkoleukinum
6 doses of IL-2 (1 × 10^6 units/m2) from -1 day every other day.
| Study group | Role | What they receive |
|---|---|---|
| NK cells + IL-2 | Experimental | After cycle of chemotherapy patient receive one intravenous infusion of expanded haploidentical NK cells on day 0. On alternate days, 6 doses of subcutaneous IL-2 is administered with start on day -1. Receives: Biological: Expanded Haploidentical Natural Killer cells; Drug: IL-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
Adverse events will be graded according to the CTCAE v4.0
Measured: 1 months
Secondary outcomes (4)
Days of persistence of adoptively-transferred haploidentical NK cells
Analysis of donor chimerism at +2, 6, 10, 14, 21, 28 days after NK infusion.
Measured: 1 months
Occurrence of disease response
Analysis of blast cells content in bone marrow by cytomorphology or detection of MRD level by flow/PCR before and after immunotherapy.
Measured: 1 months post infusion
Median time to leukocytes and platelets recovery
Days of platelets (>50x10^9/L) and leukocytes (>1x10^9/L) recovery.
Measured: 2 months post infusion
Number of T, B, NK, activated T and NK cells after immunotherapy
Analysis of T, B, NK, activated T and NK cells numbers (cells/microL) at +2, 6, 10, 14, 21, 28 days after NK infusion.
Measured: 1 months post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2020
- Study start2 Jan 2019
- Primary completion6 Jun 2021
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Acute MyeloidStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Belarusian Research Center for Pediatric Oncology, Hematology and Immunology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olga Aleinikova, Principal investigator, Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04327037
- Sponsor's protocol ID
- BelarusianPediatric_NK_Pilot
- Status last verified
- Feb 2022
- First submitted
- 18 Mar 2020
- Last updated
- 2 Mar 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Shman TV, Vashkevich KP, Migas AA, Matveyenka MA, Lasiukov YA, Mukhametshyna NS, Horbach KI, Aleinikova OV. Phenotypic and functional characterisation of locally produced natural killer cells ex vivo expanded with the K562-41BBL-mbIL21 cell line. Clin Exp Med. 2023 Oct;23(6):2551-2560. doi: 10.1007/s10238-022-00974-2. Epub 2022 Dec 17.
PubMed 36527513
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Immunotherapy With ex Vivo Expanded Haploidentical Natural Killer Cells for Leukemia
- ClinicalTrials.gov ID
- NCT04327037
- Acronym / sponsor ID
- BelarusianPediatric_NK_Pilot
- Keywords
- Immunotherapy, Natural killer cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Belarusian Research Center for Pediatric Oncology, Hematology and ImmunologyUniversity, hospital or other
- Study start
- 2 Jan 2019 (actual)
- Primary completion
- 6 Jun 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 30 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to estimate the safety of ex vivo expanded haploidentical natural killer (NK) cells for patients with leukemia.
Detailed description
Immunotherapy with natural killer (NK) cells may improve the results of treatment for patients with cancer. However, for better efficiency high doses of NK cells are required. For this purpose, NK cells were expanded in the presence of feeder K562 cells gene-modified for expression 4-1BBL and membrane bound IL-21. In the result of expansion, large number of activated NK cells are obtained.
Protocol of immunotherapy includes conditioning (fludarabine + cyclophosphamide or any other protocol of chemotherapy) followed by expanded NK cells intravenous infusion. To sustain proliferation of donor NK cells in vivo patients receive 6 doses of Il-2 every second day. 10 patients will be enrolled in phase I to test different doses of NK cells: 20, 50, 70, 100 and >100 x 10^6/kg.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NK cells + IL-2 | Experimental | Biological: Expanded Haploidentical Natural Killer cells, Drug: IL-2After cycle of chemotherapy patient receive one intravenous infusion of expanded haploidentical NK cells on day 0. On alternate days, 6 doses of subcutaneous IL-2 is administered with start on day -1. |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Relapsed acute myeloid or lymphoblastic leukemia
- Primary refractory myeloid or lymphoblastic leukemia
- Karnofsky or Lansky performance scale greater or equal to 70
- Written informed consent
- Haploidentical family donor
Key exclusion criteria (7 listed)
- Uncontrolled infection
- Severe hepatic dysfunction: SGOT or SCPT >=5x upper limit of normal for age
- Positive serology for human immunodeficiency virus (HIV)
- Pregnancy or breast feeding
- Positive serology for HIV, hepatitis B or C.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Expanded Haploidentical Natural Killer cellsOne dose (from 20x to >100x 10^6 /kg) of expanded haploidentical NK cells | Biological | NK cells + IL-2 |
| IL-2Also: Ronkoleukinum6 doses of IL-2 (1 × 10^6 units/m2) from -1 day every other day. | Drug | NK cells + IL-2 |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: 1 months
Adverse events will be graded according to the CTCAE v4.0
4 secondary outcomes
Days of persistence of adoptively-transferred haploidentical NK cells
Time frame: 1 months
Occurrence of disease response
Time frame: 1 months post infusion
Median time to leukocytes and platelets recovery
Time frame: 2 months post infusion
Number of T, B, NK, activated T and NK cells after immunotherapy
Time frame: 1 months post infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2022.
- Derived from this study: PubMed 36527513Shman TV, Vashkevich KP, Migas AA, Matveyenka MA, Lasiukov YA, Mukhametshyna NS, Horbach KI, Aleinikova OV. Phenotypic and functional characterisation of locally produced natural killer cells ex vivo expanded with the K562-41BBL-mbIL21 cell line. Clin Exp Med. 2023 Oct;23(6):2551-2560. doi: 10.1007/s10238-022-00974-2. Epub 2022 Dec 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Olga Aleinikova principal investigator
Belarussian Research Center for Pediatric Oncology, Hematology and Immunology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Expanded Haploidentical Natural Killer cells and IL-2 in people with Leukemia, Acute Myeloid and Leukemia, Acute Lymphoblastic, run by Belarusian Research Center for Pediatric Oncology, Hematology and Immunology at 1 site in Belarus.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belarus. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: 1 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04327037, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2022.