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

DLBCL Clinical Trial

Official title:

A Phase Ib, Double Blind RCT to Evaluate and Compare the PK, PD and Safety of MabThera® With TL011, in Combination With CHOP, in Subjects With CD20+ DLBCL

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01205737
• Other study ID #: NHL-TL011-102
• Status: Completed
• Phase: Phase 1
• First received: September 17, 2010
• Last updated: October 21, 2013
• Start date: September 2010
• Est. completion date: September 2013

Study information

• Verified date: October 2013
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hungary: National Institute of Pharmacy
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 186
• Est. completion date: September 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• DLBCL
• Lymphoma, B-Cell

Intervention

Biological:
• TL011
375 mg/m2 iv every 3 weeks for 8 cycles
• Rituximab
375 mg/m2 iv every 3 weeks for 8 cycles

Locations

Country	Name	City	State
Bulgaria	Teva Investigational Site 59005	Pleven
Bulgaria	Teva Investigational Site 59003	Plovdiv
Bulgaria	Teva Investigational Site 59001	Sofia
Bulgaria	Teva Investigational Site 59002	Sofia
Bulgaria	Teva Investigational Site 59004	Varna
Estonia	Teva Investigational Site 55001	Tallinn
Estonia	Teva Investigational Site 55002	Tartu
France	Teva Investigational Site 35066	Paris Cedex 13
Hungary	Teva Investigational Site 51026	Debrecen
Italy	Teva Investigational Site 30001	Firenze
Italy	Teva Investigational Site 30002	Napoli
Latvia	Teva Investigational Site 56002	Daugavpils
Latvia	Teva Investigational Site 56001	Riga
Latvia	Teva Investigational Site 56003	Riga
Poland	Teva Investigational Site 53010	Warsaw
Russian Federation	Teva Investigational Site 50011	Arkhangelsk
Russian Federation	Teva Investigational Site 50001	Chelyabinsk
Russian Federation	Teva Investigational Site 50004	Ekaterinburg
Russian Federation	Teva Investigational Site 50006	Kazan
Russian Federation	Teva Investigational Site 50014	Kursk
Russian Federation	Teva Investigational Site 50005	Moscow
Russian Federation	Teva Investigational Site 50009	Moscow
Russian Federation	Teva Investigational Site 50010	Moscow
Russian Federation	Teva Investigational Site 50003	Novosibirsk
Russian Federation	Teva Investigational Site 50017	Pyatigorsk
Russian Federation	Teva Investigational Site 50012	St. Petersburg
Russian Federation	Teva Investigational Site 50015	Tomsk
Spain	Teva Investigational Site 31005	Elche-Alicante
Spain	Teva Investigational Site 31006	Las Palmas de Gran Canaria
Spain	Teva Investigational Site 31002	Madrid
Spain	Teva Investigational Site 31001	Majadahonda-Madrid
Spain	Teva Investigational Site 31003	Valencia
Spain	Teva Investigational Site 31004	Valencia
Ukraine	Teva Investigational Site 58011	Cherkasy
Ukraine	Teva Investigational Site 58013	Dnipropetrovsk
Ukraine	Teva Investigational Site 58014	Donetsk
Ukraine	Teva Investigational Site 58017	Khmelnytskyi
Ukraine	Teva Investigational Site 58010	Kyiv
Ukraine	Teva Investigational Site 58012	Kyiv
Ukraine	Teva Investigational Site 58015	Kyiv
Ukraine	Teva Investigational Site 58016	Simferopol

Sponsors (1)

Lead Sponsor	Collaborator
Teva Pharmaceutical Industries

Countries where clinical trial is conducted

Bulgaria,  Estonia,  France,  Hungary,  Italy,  Latvia,  Poland,  Russian Federation,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC during a dosing interval for Rituximab		21 weeks	No
Secondary	PK and PD parameters		Throughout study	No