A Double-blind, Randomized Controlled Study in CD20-positive Diffuse B Cell Non-Hodgkin's Lymphoma Subjects

Phase 1

Completed

• Conditions: DLBCL
• Interventions: Biological: TL011; Biological: Rituximab

• Registration Number: NCT01205737
• Lead Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Brief Summary

This is a prospective international, multi-center, randomized, double-blind controlled study designed to assess and compare the pharmacokinetics, pharmacodynamics and the safety of MabThera® and TL011, in combination with CHOP in previously untreated patients with diffuse large B cell lymphoma.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-09
• Study First Submitted: 2010-09-17
• Study First Submitted QC: 2010-09-17
• Study First Posted: 2010-09-20
• Primary Completion: 2013-07
• Study Completion: 2013-09
• Status Verified: 2013-10
• Last Update Submitted: 2013-10-21
• Last Update Posted: 2013-10-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 186

Inclusion Criteria

• Newly diagnosed subjects with a confirmed pathologic diagnosis of diffuse large B cell non-Hodgkin's lymphoma (DLBCL) based on the 2008 World Health Organization classification.

  2.CD20+ lymphoma cells at screening

• 18-80 (inclusive) years of age at screening

• Ann Arbor Stages I-IV at screening

• Any IPI score at screening

• ECOG good performance status (0-2) at screening

• Willing and able to provide written informed consent prior to performing study procedures

• Women of childbearing potential must use effective contraceptive methods starting from screening and until 12 months following the last infusion..

Exclusion Criteria

1. Any lymphoma other than CD20+ DLBCL

2. History of indolent lymphoma

3. DLBCL with central nervous system or meningeal involvement

4. Primary gastrointestinal (MALT) lymphoma

5. Bulky disease>10 cm diagnosed by imaging at screening

6. Bone marrow involvement > 25% according to bone marrow biopsy at screening

7. Subjects previously treated with chemotherapy, radiotherapy, immunotherapy or experimental therapies for lymphoma or other malignancy

8. Hypersensitivity to active ingredients, excipients (sodium citrate, polysorbate 80, sodium chloride, sodium hydroxide, hydrochloric acid, water for injections) and murine proteins

9. Active uncontrolled infection (viral, bacterial or fungal infection) requiring systemic therapy at screening and/or at baseline visit.

10. A documented history of recurrent or chronic clinically significant infection (viral, bacterial or fungal infection)

11. Subjects with a history of tuberculosis or active tuberculosis at screening.

12. Immunodeficiency syndrome or Human immunodeficiency virus (HIV) seropositivity

13. Positive Hepatitis B surface antigen or antibodies to Hepatitis C

14. History of other cancer within the past 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of uterine cervix

15. Any major surgical procedure within 12 weeks prior to screening and between screening and baseline

16. Immunization with live viral vaccines less than 4 weeks prior to first study drug infusion, and/or planned live viral vaccination during study period.

17. Known allergic reactions against foreign proteins

18. Subjects for whom 8 cycles of CHOP might be problematic, and have the following findings/conditions, should not be enrolled:

    • Cardiac contra-indication to doxorubicin: Left ventricular ejection fraction (LVEF) < 50% according to multi-acquisition gated (MUGA) scan or 2D Echocardiogram at screening
    • Neurologic contra-indication to vincristine: (e.g., peripheral neuropathy)
    • Abnormal hepatic function at screening and/or baseline
    • AST/ALT ≥ 3 x upper normal value (ULN) or ≥ 5 x ULN in the presence of DLBCL involvement of the liver
    • Bilirubin ≥ 2 x ULN or ≥ 5 x ULN in the presence of DLBCL involvement of the liver
    • Abnormal renal function at screening and/or baseline
    • Serum creatinine ≥ 2 x ULN
    • Abnormal bone marrow function at screening and/or baseline
    • Platelets < 100x109/L
    • Neutrophils < 1.5x109/L
    • Hb < 9g/dL

19. Any other serious active disease or co-morbid medical condition (according to the investigator's decision and information provided in the Investigator Brochure of TL011)

20. Subjects who, according to the investigator, are likely to be non-compliant or uncooperative during the study.

21. Pregnant or lactating women or women that intend to get pregnant during study or within 12 months following the last infusion.

22. Treatment with any investigational drug within 90 days before planned first cycle of chemotherapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TL011	TL011	-
MabThera®	Rituximab	-

Primary Outcome Measures

Name	Time	Method
AUC during a dosing interval for Rituximab	21 weeks

Secondary Outcome Measures

Name	Time	Method
PK and PD parameters	Throughout study

Trial Locations

Locations (41)

Teva Investigational Site 59003; 🇧🇬 Plovdiv, Bulgaria

Teva Investigational Site 59002; 🇧🇬 Sofia, Bulgaria

Teva Investigational Site 59001; 🇧🇬 Sofia, Bulgaria

Teva Investigational Site 51026; 🇭🇺 Debrecen, Hungary

Teva Investigational Site 50006; 🇷🇺 Kazan, Russian Federation

Teva Investigational Site 50005; 🇷🇺 Moscow, Russian Federation

Teva Investigational Site 59004; 🇧🇬 Varna, Bulgaria

Teva Investigational Site 55001; 🇪🇪 Tallinn, Estonia

Teva Investigational Site 56002; 🇱🇻 Daugavpils, Latvia

Teva Investigational Site 56001; 🇱🇻 Riga, Latvia

Teva Investigational Site 50009; 🇷🇺 Moscow, Russian Federation

Teva Investigational Site 56003; 🇱🇻 Riga, Latvia

Teva Investigational Site 53010; 🇵🇱 Warsaw, Poland

Teva Investigational Site 50004; 🇷🇺 Ekaterinburg, Russian Federation

Teva Investigational Site 50010; 🇷🇺 Moscow, Russian Federation

Teva Investigational Site 55002; 🇪🇪 Tartu, Estonia

Teva Investigational Site 50014; 🇷🇺 Kursk, Russian Federation

Teva Investigational Site 50012; 🇷🇺 St. Petersburg, Russian Federation

Teva Investigational Site 58011; 🇺🇦 Cherkasy, Ukraine

Teva Investigational Site 50011; 🇷🇺 Arkhangelsk, Russian Federation

Teva Investigational Site 50015; 🇷🇺 Tomsk, Russian Federation

Teva Investigational Site 50001; 🇷🇺 Chelyabinsk, Russian Federation

Teva Investigational Site 50003; 🇷🇺 Novosibirsk, Russian Federation

Teva Investigational Site 31002; 🇪🇸 Madrid, Spain

Teva Investigational Site 30001; 🇮🇹 Firenze, Italy

Teva Investigational Site 30002; 🇮🇹 Napoli, Italy

Teva Investigational Site 31003; 🇪🇸 Valencia, Spain

Teva Investigational Site 31004; 🇪🇸 Valencia, Spain

Teva Investigational Site 31005; 🇪🇸 Elche-Alicante, Spain

Teva Investigational Site 59005; 🇧🇬 Pleven, Bulgaria

Teva Investigational Site 35066; 🇫🇷 Paris Cedex 13, France

Teva Investigational Site 31006; 🇪🇸 Las Palmas de Gran Canaria, Spain

Teva Investigational Site 58013; 🇺🇦 Dnipropetrovsk, Ukraine

Teva Investigational Site 58010; 🇺🇦 Kyiv, Ukraine

Teva Investigational Site 58014; 🇺🇦 Donetsk, Ukraine

Teva Investigational Site 58017; 🇺🇦 Khmelnytskyi, Ukraine

Teva Investigational Site 58012; 🇺🇦 Kyiv, Ukraine

Teva Investigational Site 50017; 🇷🇺 Pyatigorsk, Russian Federation

Teva Investigational Site 31001; 🇪🇸 Majadahonda-Madrid, Spain

Teva Investigational Site 58015; 🇺🇦 Kyiv, Ukraine

Teva Investigational Site 58016; 🇺🇦 Simferopol, Ukraine