Study of RTXM83 Plus CHOP Chemotherapy Versus a Rituximab Plus CHOP Therapy in Patients With Non Hodgkin's Lymphoma

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02268045
• Date of registration: 19/09/2014
• Prospective Registration: No
• Primary sponsor: mAbxience S.A
• Public title: Study of RTXM83 Plus CHOP Chemotherapy Versus a Rituximab Plus CHOP Therapy in Patients With Non Hodgkin's Lymphoma
• Scientific title: A Randomized, Double-blind, Phase III Study Comparing Biosimilar Rituximab (RTXM83) Plus CHOP Chemotherapy Versus a Reference Rituximab Plus CHOP (R-CHOP) in Patients With Diffuse Large B-cell Lymphoma (DLBCL) Given as First Line
• Date of first enrolment: May 2013
• Target sample size: 272
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02268045
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Brazil, Colombia, India, Indonesia, Iran, Islamic Republic of, Malaysia, Mexico, Paraguay, Philippines, Russian Federation, South Africa, Thailand

Contacts

• Name: Susana Millán, Phd
• Affiliation: mAbxience S.A

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diffuse Large B-cell Lymphoma

Intervention(s)

Biological: Mabthera

Biological: RTXM83

Primary Outcome(s)

Response Rate (RR) Achieved After Cycle 6 With RTXM83 Plus CHOP Compared to the RR Obtained With Mabthera® Plus CHOP (R-CHOP) in Patients With DLBCL [Time Frame: Tumor response assessed after Cycle 6 or at the end of treatment]

Secondary Outcome(s)

Percentage Change From Baseline in Pharmacodynamic (PD) Markers (CD19+ and CD20+ Cells) Blood Counts of RTXM83 and Mabthera® [Time Frame: Up to follow-up 3 (FU3); 9 months after last dose of treatment]

AUC 0-8 (h µg/mL) at Cycle 6 of RTXM83 and Mabthera® [Time Frame: Cycle 6 (last dose): Day 1, Day 8, Day 15 and Day 21]

Cmax (µg/mL) at Cycle 1 of RTXM83 and Mabthera® [Time Frame: Cycle 1 (first dose): Day 1 (pre-dose, mid-infusion), Day 8 and Day 15]

Cmax (µg/mL) at Cycle 6 of RTXM83 and Mabthera® [Time Frame: Cycle 6 (last dose): Day 1, Day 8, Day 15 and Day 21]

Comparable Safety Profile in Both Treatment Arms [Time Frame: Up to FU3; 9 months after last dose of treatment]

AUC 0-8 (h µg/mL) at Cycle 1 of RTXM83 and Mabthera® [Time Frame: Cycle 1 (first dose): Day 1 (pre-dose, mid-infusion), Day 8 and Day 15]

Event Free Survival (EFS) in RTXM83 Arm and Mabthera® Arm [Time Frame: Up to FU3; 9 months after last dose of treatment]

Comparable Immunogenicity Profile Between RTXM83 and Mabthera® [Time Frame: Up to FU3; 9 months after last dose of treatment]

Secondary ID(s)

RTXM83-AC-01-11

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Tecnoquimicas S.A

Nanolek LLC

Pisa® Farmacéutica

Actoverco

Innogene Kalbiotech Pte. Ltd

Key Oncologics (Pty) Ltd

Laboratorios de Productos Éticos C.E.I.S.A.

Laboratorio Elea Phoenix S.A.

Libbs Farmacêutica LTDA

Results

• Results available: Yes
• Date Posted: 26/09/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02268045