Study of RTXM83 Plus CHOP Chemotherapy Versus a Rituximab Plus CHOP Therapy in Patients With Non Hodgkin's Lymphoma
Condition: Diffuse Large B-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: RTXM83; Mabthera
Intervention description: Rituximab biosimilar (RTXM83) will be administered in combination with CHOP chemotherapy regimen (Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 up to a maximum of 2 mg on Day 1 plus Prednisone 40 mg/m2 or 100 mg per day from Day 1 to 5) at a dose of 375 mg/m2 on Day 1 of each 3 week cycle, for 6 cycles, although the administration of 2 additional cycles may be allowed.; Mabthera will be administered in combination with CHOP chemotherapy regimen (Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2 and Vincristine 1.4 mg/m2 up to a maximum of 2 mg on Day 1 plus Prednisone 40 mg/m2 or 100 mg per day from Day 1 to 5) at a dose of 375 mg/m2 on Day 1 of each 3 week cycle, for 6 cycles, although the administration of 2 additional cycles may be allowed.
Intervention MeSH terms: Rituximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 272.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Non-Hodgkin Lymphoma; DLBCL; Diffuse large b-cell lymphoma

Summary:

      This is a multicenter, double-blind, randomized study comparing the efficacy,
      pharmacokinetics (PK)/pharmacodynamics (PD), safety and immunogenicity profile of RTXM83
      (rituximab biosimilar) vs reference rituximab (MabThera®), both with CHOP, as first-line
      treatment of Diffuse-Large-B-Cell-Lymphoma (DLBCL).

      Rituximab biosimilar and MabThera® were both administered intravenously on Day 1 of each
      3-week cycle with CHOP chemotherapy for six cycles. Two additional cycles of treatment were
      permitted at the Investigator's discretion. Patients were followed up for 9 months after last
      study dose.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with measurable disease defined as existence of a unidimensional or
             bidimensional lesion greater than 2 cm in its longest diameter or malignant
             lymphocytosis greater than 5x109/L. Any other procedure for measurable disease in
             particular cases, may be allowed upon Sponsor approval

          2. Newly diagnosed patients with a confirmed pathologic diagnosis of Diffuse large B
             cell-non-Hodgkin's lymphoma (DLBCL) with untreated CD20+ receptor (CD20+). Defined by
             the local Haematopathologist at the local laboratory according to World Health
             Organization (WHO) criteria

          3. Stage II-III or IV or stage I with bulk defined by the referring physician on the
             basis of the Cotswolds modification of the Ann Arbor classification 2

          4. Age-adjusted International Prognostic Index (IPI) score 0 or 1

          5. Age ≥18 to ≤65 years of age

          6. Performance status according to Eastern Cooperative Oncology Group (ECOG) of ≤2

          7. Written informed consent obtained before starting any study-specific procedure

          8. Females of child-bearing potential must test negative on standard serum pregnancy test
             and must be willing to practice appropriate contraceptive methods for the duration of
             the study (e.g. oral contraceptive, double barrier method, intra-uterine device,
             intra-muscular contraceptive)

          9. All male patients must take adequate contraceptive precautions during the course of
             the study

        Exclusion Criteria:

          1. Life expectancy of less than three months

          2. Any other lymphoma other than CD20+ DLBCL

          3. Indolent lymphoma, Primary central nervous system (CNS) Lymphoma or gastro-intestinal
             Mucosa Associated Lymphoid Tissue (MALT) Lymphoma

          4. Known hypersensitivity to active ingredients, excipients and murine and foreign
             proteins

          5. Concurrent disease or general status that would exclude giving the treatment as
             outlined in the protocol

          6. Active uncontrolled infection requiring systemic treatment with antibiotics or
             antiviral agents at Screening or history of documented recurrent clinically
             significant infection (e.g. 2 or more viral, bacterial or fungal infections requiring
             inpatient treatment)

          7. Cardiac contra-indication to Doxorubicin therapy: non-compensated heart failure,
             dilated cardiomyopathy, coronary heart disease with ST segment depression on
             electrocardiogram (ECG), myocardial infarction in the last 6 months

          8. Neurologic contra-indication to Vincristine as it is indicated in the Summary of
             Product Characteristics (SmPC): (e.g. peripheral neuropathy)

          9. Chronic lung disease with hypoxemia measured by pulse oximetry (gasometry is not
             mandatory)

         10. Severe uncontrolled hypertension, despite optimal medical treatment

         11. Severe uncontrolled diabetes mellitus, despite optimal medical treatment

         12. Renal insufficiency (Serum Creatinine >2 x Upper Normal Limit [UNL])

         13. Hepatic insufficiency: aspartate aminotransferase (AST)/ alanine aminotransferase
             (ALT)>3 x UNL or >5 x UNL with involvement of the liver, total bilirubin >34.2 µmol/L,
             or both) not related to lymphoma

         14. Clinical signs of cerebral dysfunction

         15. Severe psychiatric disease

         16. Known human immunodeficiency virus (HIV) infection or active chronic hepatitis B or C

         17. Abnormal bone marrow function (platelets <100x109/L, neutrophils <1.5x109/L and
             Haemoglobin <9g/dL)

         18. Post-transplantation lymphoproliferative disease

         19. Pregnant or lactating women or women that intend to get pregnant during study or
             within 12 months following the last infusion

         20. Treatment with any investigational product in the 30 days period before inclusion in
             the study

         21. Prior radiotherapy to treat the DLBCL Non-Hodgkin's Lymphoma (NHL)

         22. Limitation of the patient's ability to comply with the treatment or follow-up protocol