Clinical Trials /

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

NCT03778619

Description:

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

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MG4101 Plus Rituximab Including Lymphodepletion in Patient With r/r NHL B-cell Origin
  • Official Title: Multi-center, Open-label, Phase 1/2a Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy With MG4101 Plus Rituximab in Patient With Relapsed/Refractory Non-Hodgkin's Lymphoma of B-cell Origin

Clinical Trial IDs

  • ORG STUDY ID: MG4101-NHL-P1
  • NCT ID: NCT03778619

Conditions

  • Relapsed Non Hodgkin Lymphoma
  • Refractory Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
RituximabMabtherasingle arm
FludarabineFludarasingle arm
CyclophosphamideEndoxansingle arm
MG4101(allogeneic Natural Killer cell)single arm
Interleukin-2proleukinsingle arm

Purpose

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

Detailed Description

      This trial will consist of 3 parts; Phase 1 Maximum Tolerated Dose, Phase 1 extended cohort
      and Phase 2a.

      For Phase 1, those who have a confirmed diagnosis of relapsed/refractory Non-Hodgkin's
      Lymphoma (NHL) of B-cell Origin of any subtype will be considered eligible for enrolment.
      Each cycle last approximately 28 days.

      Once the dose of MG4101 is determined from Phase 1, Phase 2a will commence whereby two
      subgroups of patients will be enrolled and will similarly receive up to 6 cycles of treatment
      with the recommended Phase 2a dose of MG4101. The 2 subgroups are patients with indolent and
      aggressive NHL of B-cell origin respectively.
    

Trial Arms

NameTypeDescriptionInterventions
single armExperimentalPhase 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/㎏ Interleukin-2 (IL-2): s.c bi-weekly with MG4101 at 1X10^6 IU/m2 per day. Rituximab: 375mg/m2. i.v. weekly for the first 2 cycles only (8 doses). monthly (3-6 cycle) Lymphodepletion: Fludarabine 20mg/m2 + Cyclophosphamide 250 mg/m2 i.v. D-3, D-2, D-1 of 1st, 3rd, and 5th cycle 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.
  • Rituximab
  • Fludarabine
  • Cyclophosphamide
  • MG4101(allogeneic Natural Killer cell)
  • Interleukin-2

Eligibility Criteria

        Inclusion Criteria:

          1. 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.

          2. 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:

               1. Relapse/Progression and is not considered as a candidate for autologous stem-cell
                  transplantation or high-dose immuno-chemotherapy with allogenic antibody
                  transplantation.

               2. Or Relapsed/progressed after high-dose immuno-chemotherapy with autologous
                  stem-cell transplantation.

               3. 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

          3. 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.

          4. Eastern Cooperative Oncology Group score 0 or 1

          5. 20 years or older. Age limit for Phase 1 is 65 and for Phase 2a 80.

          6. Expected lifespan ≥ 3 month

          7. Patients signed Informed consent form

          8. Earlier documented result that showed that the patient is positive for CD20 via
             immunophenotyping within 6 months of C1V1

          9. Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for
             clinically non-significant toxicities such as alopecia)

         10. Those patients who satisfied with following criteria in blood testing, kidney function
             test and liver function test:

               1. Absolute neutrophil count: Absolute Neutrophil Count ≥ 1,000/ µL (Growth factor
                  support at least 2 weeks prior to C1V1)

               2. Haemoglobin level ≥ 8g/㎗ (Blood transfusion at least 2 weeks prior to C1V1)

               3. Platelet count ≥75,000/µL (Growth factor support/blood transfusion at least 2
                  weeks prior to C1V1)

               4. Total bilirubin < 3.0㎎/㎗

               5. Aspartate aminotransferase(AST) or Alanine Aminotransferase(ALT) ≤ 2.5 x upper
                  normal limit (UNL)

               6. Creatinine clearance (as estimated by Cockcroft Gault) ≥ 30 mL/min

        Exclusion Criteria:

          1. Patients considered appropriate to have stem-cell transplantation after high-dose
             chemotherapy as salvage therapy.

          2. Patient with Central Nervous System(CNS) lymphoma or any involvement of the CNS.

          3. Patients who had a prior history of another malignancy over the last 5 years.

          4. Patients with impaired organ functions deemed as significant by investigators.

          5. Patients who had prior allogeneic Natural Killer cell treatment.

          6. Chronic or active infectious diseases required to be treated at the time of
             Investigational Product administration, including Cytomegalovirus(CMV) prophylactic
             therapy.

          7. Had human immunodeficiency virus (HIV)-positive serology.

          8. HBsAg or Hepatitis B virus(HBV) DNA positive or had Hepatitis C virus(HCV) antibodies

          9. Patients who received anti-CD20 cancer chemotherapy or immunoglobulin within 4 weeks
             of C1V1.

         10. Patients who received another investigational drug within 4 weeks of C1V1.

         11. Patients with acute graft-versus-host disease(GvHD) ≥Grade 3 or extensive chronic GvHD
             within 2 weeks of C1V1.

         12. High-dose stem cell support treatment carried out within 6 months of C1V1.

         13. Radioimmunotherapy within 4 weeks of C1V1.

         14. Patients with major surgery within 4 weeks of C1V1.

         15. 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.

         16. Patients on enzyme inducing agents.

         17. Patients who have a plan to have vaccination during the trial.

         18. Patients with sensitivity to Interleukin-2, cyclophosphamide or fludarabine.

         19. Patients with urinary outflow obstruction

         20. Patients with history of abnormal cardiac or pulmonary function tests in 6 months
             prior to screening visit (Clinically Significant)

         21. Patients with history of solid organ allografts

         22. Patients with pre-existing or initial presentation of autoimmune disease or
             inflammatory disorders, such as Crohn's disease, scleroderma, thyroiditis,
             inflammatory arthritis, diabetes mellitus, oculo-bulbar myasthenia gravis, crescentic
             Immunoglobulin A(IgA) glomerulonephritis, cholecystitis, cerebral vasculitis,
             Stevens-Johnson syndrome and bullous pemphigoid, due to possible exacerbation with
             IL-2

         23. Concomitant treatment with other cardiotoxic inducing agents

         24. Patients who are allergic to Rituximab, Rituximab's excipient (sodium citrate,
             polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid) or other
             proteins same as Rituximab.

         25. From the day of participation of this trial to 12 months from the day of final
             administration of Investigational Product, patients who are unable or unwilling to use
             appropriate contraceptive methods. (Condom, diaphragm, Intrauterine Device, hormonal
             oral contraceptive use, or male partner with vasectomy)

         26. Pregnant or lactating women. (Breast-feeding cannot be done within 12 months after
             final Investigational Product administration)

         27. Patients suspected to have currently known or suspected alcohol abuse or drug abuse
             according to investigator's decision.

         28. According to investigator's judgement, protocols cannot be followed.
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase I - Maximum Tolerated Dose of the dose of MG4101 in combination with Rituximab
Time Frame:28 days
Safety Issue:
Description:Dose-Limiting Toxicity assessment

Secondary Outcome Measures

Measure:Phase I - Objective Response Rate
Time Frame:1 years
Safety Issue:
Description:investigator review by Positron Emission Tomograph-CT
Measure:Phase II - Complete Response
Time Frame:up to 3 years
Safety Issue:
Description:Complete Response Rate
Measure:Phase II -Partial Response
Time Frame:up to 3 years
Safety Issue:
Description:Partial Response rate
Measure:Phase II - Overall Survival
Time Frame:up to 3 years
Safety Issue:
Description:every 12 weeks after End Of Treatment
Measure:Phase II - Time To Progression
Time Frame:up to 3 years
Safety Issue:
Description:every 12 weeks after End Of Treatment
Measure:Phase II - Time to Response
Time Frame:up to 3 years
Safety Issue:
Description:every 12 weeks after End Of Treatment

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Green Cross LabCell Corporation

Last Updated