Clinical trial NCT01205737: A Double-blind, Randomized Controlled Study in CD20-positive Diffuse B Cell Non-Hodgkin's Lymphoma Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: DLBCL
Keywords: DLBCL
pharmacokinetics
pharmacodynamics
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2010-09-20
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: AUC during a dosing interval for Rituximab
timeFrame: 21 weeks
Secondary outcomes:
measure: PK and PD parameters
timeFrame: Throughout study
Other outcomes:
Locations:
city: Pleven
country: Bulgaria
facility: Teva Investigational Site 59005
city: Plovdiv
country: Bulgaria
facility: Teva Investigational Site 59003
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59001
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59002
city: Varna
country: Bulgaria
facility: Teva Investigational Site 59004
city: Tallinn
country: Estonia
facility: Teva Investigational Site 55001
city: Tartu
country: Estonia
facility: Teva Investigational Site 55002
city: Paris Cedex 13
country: France
facility: Teva Investigational Site 35066
city: Debrecen
country: Hungary
facility: Teva Investigational Site 51026
city: Firenze
country: Italy
facility: Teva Investigational Site 30001
city: Napoli
country: Italy
facility: Teva Investigational Site 30002
city: Daugavpils
country: Latvia
facility: Teva Investigational Site 56002
city: Riga
country: Latvia
facility: Teva Investigational Site 56001
city: Riga
country: Latvia
facility: Teva Investigational Site 56003
city: Warsaw
country: Poland
facility: Teva Investigational Site 53010
city: Arkhangelsk
country: Russian Federation
facility: Teva Investigational Site 50011
city: Chelyabinsk
country: Russian Federation
facility: Teva Investigational Site 50001
city: Ekaterinburg
country: Russian Federation
facility: Teva Investigational Site 50004
city: Kazan
country: Russian Federation
facility: Teva Investigational Site 50006
city: Kursk
country: Russian Federation
facility: Teva Investigational Site 50014
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50005
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50009
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50010
city: Novosibirsk
country: Russian Federation
facility: Teva Investigational Site 50003
city: Pyatigorsk
country: Russian Federation
facility: Teva Investigational Site 50017
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 50012
city: Tomsk
country: Russian Federation
facility: Teva Investigational Site 50015
city: Elche-Alicante
country: Spain
facility: Teva Investigational Site 31005
city: Las Palmas de Gran Canaria
country: Spain
facility: Teva Investigational Site 31006
city: Madrid
country: Spain
facility: Teva Investigational Site 31002
city: Majadahonda-Madrid
country: Spain
facility: Teva Investigational Site 31001
city: Valencia
country: Spain
facility: Teva Investigational Site 31003
city: Valencia
country: Spain
facility: Teva Investigational Site 31004
city: Cherkasy
country: Ukraine
facility: Teva Investigational Site 58011
city: Dnipropetrovsk
country: Ukraine
facility: Teva Investigational Site 58013
city: Donetsk
country: Ukraine
facility: Teva Investigational Site 58014
city: Khmelnytskyi
country: Ukraine
facility: Teva Investigational Site 58017
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 58010
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 58012
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 58015
city: Simferopol
country: Ukraine
facility: Teva Investigational Site 58016
Study officials:
affiliation: Hospital Universitario Puerta de Hierro
name: Mariano Provencio, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: