Study of RTXM83 plus CHOP chemotherapy versus a rituximab plus CHOP therapy in patients with Non Hodgkin?s lymphoma

• Register: ISRCTN
• Last refreshed on: 4 March 2019
• Main ID: ISRCTN26918647
• Date of registration: 18/07/2013
• Prospective Registration: No
• Primary sponsor: mAbxience (Switzerland)
• 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: 30/11/2012
• Target sample size: 250
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN26918647
• Study type: Interventional
• Study design: Prospective phase III multicenter double-blind randomized study (Treatment)
• Phase: Phase III

Countries of recruitment

Argentina, Brazil, Colombia, India, Indonesia, Mexico, Paraguay, South Africa, Venezuela

Contacts

• Name: Susana Millan

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 large B cell-non-Hodgkin?s lymphoma (DLBCL) with untreated CD20+. Defined by the local Haematopathologist at the local laboratory according to 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 (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 SmPC: (e.g. peripheral neuropathy)
9. Chronic lung disease with hypoxemia measured by saturometer (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>2xUNL)
13. Hepatic insufficiency (aspartate aminotransferase [AST]/alanine aminotransferase [ALT] >3xUNL or >5xUNL 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 NHL
22. Limitation of the patient?s ability to comply with the treatment or follow-up protocol


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Diffuse large b-cell lymphoma (DLBCL)
Cancer
Diffuse large B-cell lymphoma

Intervention(s)

RTXM83 and Rituximab will be administered as : 375 mg/m2 I.V., every 3 weeks on Day 1 of the CHOP regimen, with a total of 6 cycles.

Primary Outcome(s)

Response Rate

Secondary Outcome(s)

1. To evaluate Event Free Survival (EFS) in both treatment arms
2. To evaluate Safety in both arms
3. To demonstrate comparable pharmacokinetics of RTXM83 and Rituximab
4. To demonstrate comparable pharmacodynamics
5. To compare immunogenicity between both arms

Secondary ID(s)

RTXM83-AC-01-11

Source(s) of Monetary Support

A partnership has been established between mAbxience SA (Switzerland) and other pharmaceutical companies for the development of this large, phase III, multicentre clinical trial with this product, each company contributing to support the complete cost of the trial

Ethics review

Status:
Approval date:
Contact:

- 7-May-2012 ? Ref No. NAP ? Comité Independiente de Ética para Ensayos en Farmacología Clínica (FEFYM), Buenos Aires, Argentina - 31-May-2012 ? Ref No. NAP ? Consejo de Bioética. Sistema Provincial de Salud. Ministerio de Salud Pública de la Provincia de Tucumán, Argentina - 19-Jul-2012 ? Ref No. HP-422 ? Comité Institucional de Ética de Investigación en Salud ? Hospital Privado-Centro Médico de Córdoba - 24-Oct-20

Results

• Results available: Yes
• Date Completed: 30/05/2014