MG4101 for Refractory or Relapsed AML

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: MG4101

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 Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sang-A Kim, MD; Phone Number: +82 10 3026 0621; Email: sanga0906@naver.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MG4101; 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 frequencyIntravenous over 1 hourDay 4, Day 11, Day 18 of each cycle	Drug: MG4101; Administration of study drug (MG4101) for the patients with refractory or relapsed acute myeloid leukemia (Single arm); Other Names: Allogeneic natural killer cell

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Youngil Koh, MD, Seoul National University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2017
• Primary Completion (Actual): March 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: November 17, 2017
• First Submitted That Met QC Criteria: November 17, 2017
• First Posted (Actual): November 21, 2017

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 16, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Allogeneic natural killer cell, MG4101
• Other Study ID Numbers: H-1705-065-853

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make individual participant data

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No