MG4101 for Refractory or Relapsed AML

Study Overview
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Brief Summary
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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
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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.

Official Title
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Pilot Study of Safety and Efficacy of Lymphodepletion Followed by MG4101 Administered Intravenously to Patients With Refractory or Relapsed AML

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: MG4101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: Acute promyelocytic leukemia Central nervous system involvement of the leukemia Hypersensitivity to IL-2 Previous cell therapy Impaired major organ function

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single center, single arm, open-labeled phase 2 trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MG4101<br>MG4101 administration (Not yet commercialized) 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) Duration and frequency Intravenous over 1 hour Day 4, Day 11, Day 18 of each cycle | Drug: MG4101<br>* Administration of study drug (MG4101) for the patients with refractory or relapsed acute myeloid leukemia (Single arm)<br>* Other names: Allogeneic natural killer cell;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | After completion of 2 cycles of treatment (Day 56 from the initiation of the treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | From the initiation of the study to the death of any cause or censoring | At the end of the study (Day 112 from the initiation of the treatment) | 
| Duration of complete remission | Cumulative incidence of relapse | At the end of the study treatment (Day 112 from the initiation of the treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allogeneic natural killer cell, MG4101