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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier:
NCT01205737
First received: September 17, 2010
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
DLBCL
Biological: TL011
Biological: Rituximab
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • AUC during a dosing interval for Rituximab [ Time Frame: 21 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PK and PD parameters [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 186
Study Start Date: September 2010
Study Completion Date: September 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TL011 Biological: TL011
375 mg/m2 iv every 3 weeks for 8 cycles
Active Comparator: MabThera® Biological: Rituximab
375 mg/m2 iv every 3 weeks for 8 cycles

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01205737

  Show 41 Study Locations
Sponsors and Collaborators
Teva Pharmaceutical Industries
Investigators
Principal Investigator: Mariano Provencio, MD, PhD Hospital Universitario Puerta de Hierro
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries
ClinicalTrials.gov Identifier: NCT01205737     History of Changes
Other Study ID Numbers: NHL-TL011-102
Study First Received: September 17, 2010
Last Updated: October 21, 2013
Health Authority: Hungary: National Institute of Pharmacy

Keywords provided by Teva Pharmaceutical Industries:
DLBCL
pharmacokinetics
pharmacodynamics

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on October 02, 2014