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To determine the efficacy and safety of combined therapy of determined MG4101 dose and Rituximab.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| single arm | Experimental |
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rituximab | Drug | weekly administration of Rituximab 375mg/m2 during cycle 1 and 2, monthly administration from cycle 3(up to cycle 6) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Phase I - Objective Response Rate | investigator review by Positron Emission Tomograph-CT | 1 years |
| Phase II - Complete Response | Complete Response Rate |
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Inclusion Criteria:
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.
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
20 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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Won Seog Kim, Dr. | Samsung Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asan Medical Center | Seoul | South Korea | ||||
| Samsung Medical Center |
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| 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 |
|
|
| 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 |
|
|
| MG4101(allogeneic Natural Killer cell) | Biological | administration every fortnight for each cycle, beginning with the 1st dose of rituximab for that cycle. |
|
| Interleukin-2 | Drug | 1 x 10^6 IU/m2, together with MG4101 |
|
|
| up to 3 years |
| Phase II -Partial Response | Partial Response rate | up to 3 years |
| Phase II - Overall Survival | every 12 weeks after End Of Treatment | up to 3 years |
| Phase II - Time To Progression | every 12 weeks after End Of Treatment | up to 3 years |
| Phase II - Time to Response | every 12 weeks after End Of Treatment | up to 3 years |
| Seoul |
| South Korea |
| Seoul National Univ. Hospital | Seoul | South Korea |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D003520 | Cyclophosphamide |
| D007376 | Interleukin-2 |
| C082598 | aldesleukin |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D007378 | Interleukins |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D008222 | Lymphokines |
| D001685 | Biological Factors |
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