Acute Myeloid LeukemiaPhase 2NCT03349502
MG4101 for Refractory or Relapsed AML
A Phase 2 study testing MG4101 in people with Acute Myeloid Leukemia, run by Seoul National University Hospital at 1 site in South Korea.
Trial summary
This study is a single center, single arm, open-labeled phase 2 clinical study. The aim of this study is to investigate the efficacy and safety of allogeneic natural killer cell (MG4101). After lymphodepletion with fludarabine and cyclophosphamide, the patient will receive MG4101. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- MG4101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Nov 2017to 30 Apr 2020
- Phase
- Phase 2
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18 to 65
- Eastern Cooperative Oncology Group (ECOG) performance status 0,1,2
- Informed consent
- Diagnosed with acute myeloid leukemia by 2016 WHO criteria
- Failure to achieve complete remission after the second line of standard chemotherapy
- Relapse after the second line of standard chemotherapy and not eligible for the allogeneic stem cell transplantation
- Adequate major organ function
Who cannot join
- Acute promyelocytic leukemia
- Central nervous system involvement of the leukemia
- Hypersensitivity to IL-2
- Previous cell therapy
- Impaired major organ function
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot Study of Safety and Efficacy of Lymphodepletion Followed by MG4101 Administered Intravenously to Patients With Refractory or Relapsed AML
This study is a single center, single arm, open-labeled phase 2 clinical study. The aim of this study is to investigate the efficacy and safety of allogeneic natural killer cell (MG4101). After lymphodepletion with fludarabine and cyclophosphamide, the patient will receive MG4101. Each cycle consists of 28 days, and a total of 2 cycles of MG4101 will be administered with IL-2 to activate the study drug. The efficacy of MG4101 will be evaluated after 8 weeks from the first day of treatment. We will evaluate the safety of the drug measuring the vital sign, laboratory tests, and adverse events.
Read the detailed description
Acute myeloid leukemia is a hematologic malignancy of myeloid lines leukocyte. In Korea, acute leukemia accounts for 87% of all leukemia and the incidence of acute myeloid leukemia is twice as high as acute lymphoblastic leukemia. The general treatment strategy for AML has not changed over the past 30 years. In adult AML, about 70 to 80% of the patients achieve complete remission after the intensive induction chemotherapy, but disease recurrence is relatively common. After the recurrence, the patients with good physical condition receive intensive salvage chemotherapy followed by allogeneic hematopoietic stem cell transplantation. But even with the intensive treatment, the long-term survival rate is only about 25%.
MG4101 is the natural killer (NK) cell product that is activated in vitro after obtaining through leukapheresis from a healthy donor. The allogeneic NK cell is well known to have anti-leukemic effect in allogeneic stem cell transplantation. As it is widely reported that the lymphodepletion is essential in adoptive cell transfer therapy, MG4101 will be administered after the conditioning with cyclophosphamide and fludarabine. And after the infusion of MG4101, IL-2 will be infused together to activate the study drug.
In the dose-finding phase 1 study of MG4101 (NCT01212341), the maximal tolerated dose was estimated to exceed 3x10^7 cells/kg. The patients will receive 2.0x10^9 to 5.0x10^6 cells in each cycle, based on the weight.
The protocol is as follows:
Cyclophosphamide and fludarabine will be administered at the dose of 250 mg/m2/day and 20 mg/m2/day, respectively, for 3 days from the start of the treatment. On the 4th, 11th and 18th day, the study drug, MG4101, will be administered intravenously, followed by 3 days of IL-2. The response will be assessed on the 28th, 56th and 112th day. The adverse event will be observed for 56 days after the initiation of the treatment.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- MG4101
- Keywords
- Allogeneic natural killer cell, MG4101
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MG4101Drug
Also called Allogeneic natural killer cell
Administration of study drug (MG4101) for the patients with refractory or relapsed acute myeloid leukemia (Single arm)
| Study group | Role | What they receive |
|---|---|---|
| MG4101 | Experimental | MG4101 administration (Not yet commercialized)
1. Dosage Bwt<50 : 2.0 x109 cells (2 bags) 50≤Bwt<70 : 3.0 x109 cells (3 bags) 70≤Bwt<100 : 4.0 x109 cells (4 bags) Bwt≥100 : 5.0 x109 cells (5 bags)
2. Duration and frequency
* Intravenous over 1 hour
* Day 4, Day 11, Day 18 of each cycle Receives: Drug: MG4101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate
Sum of complete remission (less than 5% of blast in normocellular or hypercellular bone marrow, no remnant leukemic cell or chloroma, absolute neutrophile count more than 1x10^9/L, platelet count more than 100x10^9/L) and complete remission with incomplete blood count recovery (less than 5% of blast in normocellular or hypercellular bone marrow with acute neutrophil count less than 1x10^9/L or platelet count less than 100x10^9/L)
Measured: After completion of 2 cycles of treatment (Day 56 from the initiation of the treatment)
Secondary outcomes (2)
Overall survival
From the initiation of the study to the death of any cause or censoring
Measured: At the end of the study (Day 112 from the initiation of the treatment)
Duration of complete remission
Cumulative incidence of relapse
Measured: At the end of the study treatment (Day 112 from the initiation of the treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2017
- Study start1 Nov 2017
- Primary completion30 Mar 2020
- Study completion30 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single center, single arm, open-labeled phase 2 trial
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, YOUNGIL KOH, Seoul National University Hospital
- Investigators
- Youngil Koh, MD, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03349502
- Sponsor's protocol ID
- H-1705-065-853
- Status last verified
- Apr 2023
- First submitted
- 17 Nov 2017
- Last updated
- 18 Apr 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to make individual participant data
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Safety and Efficacy of Lymphodepletion Followed by MG4101 Administered Intravenously to Patients With Refractory or Relapsed AML
- ClinicalTrials.gov ID
- NCT03349502
- Acronym / sponsor ID
- H-1705-065-853
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Allogeneic natural killer cell, MG4101
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 30 Mar 2020 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 21 Nov 2017 (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.
This study is a single center, single arm, open-labeled phase 2 clinical study. The aim of this study is to investigate the efficacy and safety of allogeneic natural killer cell (MG4101). After lymphodepletion with fludarabine and cyclophosphamide, the patient will receive MG4101. Each cycle consists of 28 days, and a total of 2 cycles of MG4101 will be administered with IL-2 to activate the study drug. The efficacy of MG4101 will be evaluated after 8 weeks from the first day of treatment. We will evaluate the safety of the drug measuring the vital sign, laboratory tests, and adverse events.
Detailed description
Acute myeloid leukemia is a hematologic malignancy of myeloid lines leukocyte. In Korea, acute leukemia accounts for 87% of all leukemia and the incidence of acute myeloid leukemia is twice as high as acute lymphoblastic leukemia. The general treatment strategy for AML has not changed over the past 30 years. In adult AML, about 70 to 80% of the patients achieve complete remission after the intensive induction chemotherapy, but disease recurrence is relatively common. After the recurrence, the patients with good physical condition receive intensive salvage chemotherapy followed by allogeneic hematopoietic stem cell transplantation. But even with the intensive treatment, the long-term survival rate is only about 25%.
MG4101 is the natural killer (NK) cell product that is activated in vitro after obtaining through leukapheresis from a healthy donor. The allogeneic NK cell is well known to have anti-leukemic effect in allogeneic stem cell transplantation. As it is widely reported that the lymphodepletion is essential in adoptive cell transfer therapy, MG4101 will be administered after the conditioning with cyclophosphamide and fludarabine. And after the infusion of MG4101, IL-2 will be infused together to activate the study drug.
In the dose-finding phase 1 study of MG4101 (NCT01212341), the maximal tolerated dose was estimated to exceed 3x10^7 cells/kg. The patients will receive 2.0x10^9 to 5.0x10^6 cells in each cycle, based on the weight.
The protocol is as follows:
Cyclophosphamide and fludarabine will be administered at the dose of 250 mg/m2/day and 20 mg/m2/day, respectively, for 3 days from the start of the treatment. On the 4th, 11th and 18th day, the study drug, MG4101, will be administered intravenously, followed by 3 days of IL-2. The response will be assessed on the 28th, 56th and 112th day. The adverse event will be observed for 56 days after the initiation of the treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single center, single arm, open-labeled phase 2 trial
| Arm | Type | Receives |
|---|---|---|
| MG4101 | Experimental | Drug: MG4101MG4101 administration (Not yet commercialized) 1. Dosage Bwt<50 : 2.0 x109 cells (2 bags) 50≤Bwt<70 : 3.0 x109 cells (3 bags) 70≤Bwt<100 : 4.0 x109 cells (4 bags) Bwt≥100 : 5.0 x109 cells (5 bags) 2. Duration and frequency * Intravenous over 1 hour * Day 4, Day 11, Day 18 of each cycle |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age between 18 to 65
- Eastern Cooperative Oncology Group (ECOG) performance status 0,1,2
- Informed consent
- Diagnosed with acute myeloid leukemia by 2016 WHO criteria
- Failure to achieve complete remission after the second line of standard chemotherapy
Key exclusion criteria (5 listed)
- Acute promyelocytic leukemia
- Central nervous system involvement of the leukemia
- Hypersensitivity to IL-2
- Previous cell therapy
- Impaired major organ function
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 |
|---|---|---|
| MG4101Also: Allogeneic natural killer cellAdministration of study drug (MG4101) for the patients with refractory or relapsed acute myeloid leukemia (Single arm) | Drug | MG4101 |
Primary outcome
Overall response rate
Time frame: After completion of 2 cycles of treatment (Day 56 from the initiation of the treatment)
Sum of complete remission (less than 5% of blast in normocellular or hypercellular bone marrow, no remnant leukemic cell or chloroma, absolute neutrophile count more than 1x10^9/L, platelet count more than 100x10^9/L) and complete remission with incomplete blood count recovery (less than 5% of blast in normocellular or hypercellular bone marrow with acute neutrophil count less than 1x10^9/L or platelet count less than 100x10^9/L)
2 secondary outcomes
Overall survival
Time frame: At the end of the study (Day 112 from the initiation of the treatment)
Duration of complete remission
Time frame: At the end of the study treatment (Day 112 from the initiation of the treatment)
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 18 Apr 2023.
- Individual participant dataSharing planned: No. There is no plan to make individual participant data
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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.
Youngil Koh, MD principal investigator
Seoul National University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MG4101 in people with Acute Myeloid Leukemia, run by Seoul National University Hospital at 1 site in South Korea.
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 7 inclusion and 5 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 18 Apr 2023. 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 South Korea. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Overall response rate (time frame: After completion of 2 cycles of treatment (Day 56 from the initiation of the treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Apr 2023.