MG4101 Plus Rituximab Including Lymphodepletion in Patient With r/r NHL B-cell Origin

NCT03778619 | Unknown Phase 1 DMC

• 1 other identifier: MG4101-NHL-P1
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

To determine the efficacy and safety of combined therapy of determined MG4101 dose and Rituximab.

Conditions

Relapsed Non Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Phase I - Maximum Tolerated Dose of the dose of MG4101 in combination with Rituximab

  Dose-Limiting Toxicity assessment

  28 days

• Phase II - Objective Response Rate

  central review by Positron Emission Tomograph-CT

  up to 3 years

Secondary Outcomes (6)

• Phase I - Objective Response Rate

  1 years

• Phase II - Complete Response

  up to 3 years

• Phase II -Partial Response

  up to 3 years

• Phase II - Overall Survival

  up to 3 years

• Phase II - Time To Progression

  up to 3 years

Study Arms (1)

single arm

EXPERIMENTAL

1. Phase 1 1. MG4101 (Allogeneic Natural Killer cell): i.v bi-weekly * Group 1: 1 x 10\^7 cells/㎏ * Group 2: 3 x 10\^7 cells/㎏ * Group 3: 9 x 10\^7 cells/㎏ 2. Interleukin-2 (IL-2): s.c bi-weekly with MG4101 at 1X10\^6 IU/m2 per day. 3. Rituximab: 375mg/m2. i.v. weekly for the first 2 cycles only (8 doses). monthly (3-6 cycle) 4. Lymphodepletion: Fludarabine 20mg/m2 + Cyclophosphamide 250 mg/m2 i.v. D-3, D-2, D-1 of 1st, 3rd, and 5th cycle 2. Phase 2a Administration of recommended dosage of MG4101 determined from Phase 1 will be applied in Phase 2a. Dosage regimens for lymphodepletion, IL-2 and Rituximab will be the same as Phase 1.

Drug: Rituximab; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: MG4101(allogeneic Natural Killer cell); Drug: Interleukin-2

Interventions

Rituximab DRUG

weekly administration of Rituximab 375mg/m2 during cycle 1 and 2, monthly administration from cycle 3(up to cycle 6)

Also known as: Mabthera

single arm

Fludarabine DRUG

administration of fludarabine 20mg/m2 for 3 consecutive days starting at 3 days before the 1st, 3rd, and 5th cycle of the first rituximab infusion for that cycle

Also known as: Fludara

single arm

Cyclophosphamide DRUG

administration of fludarabine 250mg/m2 for 3 consecutive days starting at 3 days before the 1st, 3rd, and 5th cycle of the first rituximab infusion for that cycle

Also known as: Endoxan

single arm

MG4101(allogeneic Natural Killer cell) BIOLOGICAL

administration every fortnight for each cycle, beginning with the 1st dose of rituximab for that cycle.

single arm

Interleukin-2 DRUG

1 x 10\^6 IU/m2, together with MG4101

Also known as: proleukin

single arm

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with relapsed or refractory NHL of B-cell origin (mature B cell lymphoma according to WHO)\* who are not considered candidates for intensive anti-lymphoma therapy.
• Patients must have received at least 1 prior systemic treatment including anti-CD20 therapy but have received no more than 4 systemic treatments and have:
• Relapse/Progression and is not considered as a candidate for autologous stem-cell transplantation or high-dose immuno-chemotherapy with allogenic antibody transplantation.
• Or Relapsed/progressed after high-dose immuno-chemotherapy with autologous stem-cell transplantation.
• Or Relapsed/progressed after homoplastic stem-cell transplantation performed at least 12 weeks ago from C1V1.
• For Phase 1 - Any subtype can be enrolled. For Phase 2a - Only below subtype can be enrolled in each group. I. Indolent B-cell NHL: Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Mantle Cell Lymphoma and Marginal Zone Lymphoma II. Aggressive B-cell NHL: Diffuse Large B-cell Lymphoma De novo and Diffuse Large B-cell Lymphoma transformed
• According to Positron Emission Tomograph(PET)-CT screening, patients having lesion/nodules ≥1 with major axis longer than 1.5 cm and the boundaries are clearly shown.
• Eastern Cooperative Oncology Group score 0 or 1
• years or older. Age limit for Phase 1 is 65 and for Phase 2a 80.
• Expected lifespan ≥ 3 month
• Patients signed Informed consent form
• Earlier documented result that showed that the patient is positive for CD20 via immunophenotyping within 6 months of C1V1
• Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia)
• Those patients who satisfied with following criteria in blood testing, kidney function test and liver function test:
• Absolute neutrophil count: Absolute Neutrophil Count ≥ 1,000/ µL (Growth factor support at least 2 weeks prior to C1V1)

You may not qualify if:

• Patients considered appropriate to have stem-cell transplantation after high-dose chemotherapy as salvage therapy.
• Patient with Central Nervous System(CNS) lymphoma or any involvement of the CNS.
• Patients who had a prior history of another malignancy over the last 5 years.
• Patients with impaired organ functions deemed as significant by investigators.
• Patients who had prior allogeneic Natural Killer cell treatment.
• Chronic or active infectious diseases required to be treated at the time of Investigational Product administration, including Cytomegalovirus(CMV) prophylactic therapy.
• Had human immunodeficiency virus (HIV)-positive serology.
• HBsAg or Hepatitis B virus(HBV) DNA positive or had Hepatitis C virus(HCV) antibodies
• Patients who received anti-CD20 cancer chemotherapy or immunoglobulin within 4 weeks of C1V1.
• Patients who received another investigational drug within 4 weeks of C1V1.
• Patients with acute graft-versus-host disease(GvHD) ≥Grade 3 or extensive chronic GvHD within 2 weeks of C1V1.
• High-dose stem cell support treatment carried out within 6 months of C1V1.
• Radioimmunotherapy within 4 weeks of C1V1.
• Patients with major surgery within 4 weeks of C1V1.
• Patients required to have treatment as having severe diseases such as severe heart failure or uncontrolled severe heart disease and considered not to be appropriate to participate in this trial by investigator's decision.

Sponsors & Collaborators

• GC Cell Corporation: lead

Study Sites (3)

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National Univ. Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Rituximab; fludarabine; fludarabine phosphate; Cyclophosphamide; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Lymphokines; Biological Factors

Study Officials

• Won Seog Kim, Dr.

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2018
• First Posted: December 19, 2018
• Study Start: November 28, 2018
• Primary Completion: April 20, 2020
• Study Completion: October 30, 2020
• Last Updated: July 28, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3)