Study of VELCADE and Rituximab in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma - Full Text View

Purpose

The purpose of this study is to determine if the combination of VELCADE and rituximab improves progression free survival relative to rituximab alone in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (B-NHL) who never received rituximab or who have previously responded to rituximab. This is an international study being conducted in the United States and in many countries around the world. A complete list of study locations is listed below.

Condition	Intervention	Phase
Non-Hodgkin's Lymphoma	Drug: Bortezomib + Rituximab Drug: Rituximab	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Randomized, Open-Label, Multicenter Study of VELCADE With Rituximab or Rituximab Alone in Subjects With Relapsed or Refractory, Rituximab Naive or Sensitive Follicular B-cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Rituximab Bortezomib

Genetic and Rare Diseases Information Center resources: Lymphosarcoma B-cell Lymphoma

U.S. FDA Resources

Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:

Progression Free Survival [ Time Frame: Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months. ] [ Designated as safety issue: No ]
Progression free survival is defined as time from randomization to progressive disease or death due to any cause, whichever occurs first.

Secondary Outcome Measures:

Overall Response Rate [ Time Frame: Subjects are followed until progressive disease/death or the end of the study. The median follow up time is 33.9 months. ] [ Designated as safety issue: No ]
Overall response rate is defined as Complete Response (CR) + Complete Response Unconfirmed (CRu) + Partial Response (PR) using International Working Group Criteria (IWGC) and Independent Radiographic Review results and clinical results. The IWGC CR requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms, and normalization of lactic dehydrogenase and bone marrow involvement. CRu requires more than 75% reduction in sum of product of nodes (SPD). PR requires moer than 50% reduction in SPD.


Enrollment:	676
Study Start Date:	March 2006
Study Completion Date:	July 2010
Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Bortezomib + Rituximab	Drug: Bortezomib + Rituximab VELCADE for Injection will be administered weekly on Days 1,8,15, and 22 of a 35-day cycle in combination with 4 doses of rituximab once a week on Days 1,8,15, and 22 of Cycle 1 and in combination with a single dose of rituximab on Day 1 of Cycles 2 to 5.
Active Comparator: Rituximab	Drug: Rituximab rituximab once a week on Days 1,8,15, and 22 of Cycle 1, and as a single dose on Day 1 of Cycles 2 to 5 (for a total of 8 doses).

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

Man or woman and age 18 years or older
Diagnosis of follicular B-NHL of the following subtypes (World Health Organization [WHO] classification 1997): follicular lymphoma (FL) (Grades 1 and 2).
Documented relapse or progression following prior antineoplastic treatment. New lesions or objective evidence of progression of existing lesions must document relapse or progression following the previous therapy.

If any prior regimen included rituximab, the subject must have responded (complete response [CR], unconfirmed complete response [CRu], partial response [PR]), and the time to progression (TTP) from the first dose of rituximab must have been 6 months or more.

At least 1 measurable tumor mass (greater than 1.5 cm in the longest dimension and greater than 1.0 cm in the short axis) that has not been previously irradiated, or has grown since previous irradiation
In the opinion of the investigator the decision to initiate treatment is justified to manage the subject's lymphoma
No active central nervous system lymphoma
Eastern Cooperative Oncology Group [ECOG] status ≤ 2
Female subjects must be postmenopausal (for at least 6 months), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening.
Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
In countries where health authorities have approved the pharmacogenomic testing, subjects or their legally acceptable representatives must have signed a separate informed consent that they agree to participate in the genetic part and protein testing part of the study; participation in the genetic and protein testing component is mandatory for pharmacogenomics testing, but optional for serum protein testing and future testing.

Exclusion Criteria:

Potential subjects who meet any of the following criteria will be excluded from participating in the study:

Diagnosed or treated for a malignancy other than NHL within 1 year of randomization, or who were previously diagnosed with a malignancy other than NHL and have any radiographic or biochemical marker evidence of malignancy. Subjects with completely resected basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy are not excluded.
Clinical evidence of a transformation from indolent NHL to a more aggressive form of NHL.
History of disallowed therapies:
- Prior treatment with VELCADE
- Antineoplastic (including unconjugated therapeutic antibodies), experimental, or radiation therapy within 3 weeks before randomization
- Nitrosoureas within 6 weeks before randomization
- Radioimmunoconjugates or toxin immunoconjugates within 10 weeks before randomization
- Stem cell transplant within 6 months before randomization
- Major surgery within 2 weeks before randomization
Residual toxic effects of previous therapy or surgery of Grade 3 or worse
Peripheral neuropathy or neuropathic pain of Grade 2 or worse
Have received an experimental drug or used an experimental medical device within 21 days before the planned start of treatment.
History of allergic reaction attributable to compounds containing boron or mannitol
Known anaphylaxis or immunoglobulin E (IgE)-mediated hypersensitivity to murine proteins or to any component of rituximab including polysorbate 80 and sodium citrate dihydrate
Concurrent treatment with another investigational agent
Female subject who is pregnant or breast-feeding

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: NCT00312845

Show 206 Study Locations

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators


Study Director:	Medical Monitor	Millennium Pharmaceuticals, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zinzani PL, Khuageva NK, Wang H, Garicochea B, Walewski J, Van Hoof A, Soubeyran P, Caballero D, Buckstein R, Esseltine DL, Theocharous P, Enny C, Zhu E, Elsayed YA, Coiffier B. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naïve or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012 Oct 22;5:67. doi: 10.1186/1756-8722-5-67.

Coiffier B, Osmanov EA, Hong X, Scheliga A, Mayer J, Offner F, Rule S, Teixeira A, Walewski J, de Vos S, Crump M, Shpilberg O, Esseltine DL, Zhu E, Enny C, Theocharous P, van de Velde H, Elsayed YA, Zinzani PL; LYM-3001 study investigators. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011 Aug;12(8):773-84. doi: 10.1016/S1470-2045(11)70150-4. Epub 2011 Jul 1.


Responsible Party:	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00312845 History of Changes
Other Study ID Numbers:	26866138-LYM-3001
Study First Received:	April 7, 2006
Results First Received:	June 29, 2011
Last Updated:	June 19, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Millennium Pharmaceuticals, Inc.:


B-cell Non-Hodgkin's Lymphoma

Additional relevant MeSH terms:


Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders	Immune System Diseases Rituximab Bortezomib Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents

ClinicalTrials.gov processed this record on September 29, 2016