MG4101 for Refractory or Relapsed AML

• ClinicalTrials.gov Identifier: NCT03349502
• Recruitment Status: Unknown
• First Posted: November 21, 2017
• Last Update Posted: November 21, 2017
• Sponsor: Seoul National University Hospital
• Information provided by (Responsible Party): Youngil Koh, Seoul National University Hospital

Study Description

Brief 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. 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.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia	Drug: MG4101	Phase 2

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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single center, single arm, open-labeled phase 2 trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Study of Safety and Efficacy of Lymphodepletion Followed by MG4101 Administered Intravenously to Patients With Refractory or Relapsed AML
• Actual Study Start Date: November 1, 2017
• Estimated Primary Completion Date: June 17, 2019
• Estimated Study Completion Date: January 1, 2020

Arms and Interventions

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 frequency Intravenous over 1 hour Day 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 Name: Allogeneic natural killer cell

Outcome Measures

Primary Outcome Measures :

1. 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)

Secondary Outcome Measures :

1. Overall survival [ Time Frame: At the end of the study (Day 112 from the initiation of the treatment) ]
   From the initiation of the study to the death of any cause or censoring
2. Duration of complete remission [ Time Frame: At the end of the study treatment (Day 112 from the initiation of the treatment) ]
   Cumulative incidence of relapse

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Sang-A Kim, MD; +82 10 3026 0621; sanga0906@naver.com

Locations

Korea, Republic of

Seoul National University Hospital; Recruiting

Seoul, Korea, Republic of, 03080

Contact: Sang-A Kim, MD +82 10 3026 0621 sanga0906@naver.com

Principal Investigator: Youngil Koh, MD

Sub-Investigator: Sung soo Yoon, MD, PhD

Sub-Investigator: In ho Kim, MD

Sub-Investigator: Dong-Yeop Shin, MD

Sponsors and Collaborators

Seoul National University Hospital

Investigators

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

More Information

• Responsible Party: Youngil Koh, Assistant Professor, Seoul National University Hospital
• ClinicalTrials.gov Identifier: NCT03349502
• Other Study ID Numbers: H-1705-065-853
• First Posted: November 21, 2017
• Last Update Posted: November 21, 2017
• Last Verified: November 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: There is no plan to make individual participant data

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Youngil Koh, Seoul National University Hospital:

Allogeneic natural killer cell, MG4101