A Phase 2 Study of Velcade™ in Subjects With Relapsed or Refractory Follicular B-Cell Lymphoma

NCT ID: NCT00136591

Last Updated: 2010-10-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2010-01-31

Brief Summary

This is a prospective, randomized, sequential, international, multicentric, 2-arm, non-comparative, open-label, 2-stage clinical study to determine disease response rates to Velcade™ therapy in subjects who have relapsed or refractory follicular B-cell lymphoma.

Qualitative comparisons of the 2 treatment arms based on safety, efficacy and dosing convenience will be made in order to recommend a dose schedule for further clinical study.

Detailed Description

This is a prospective, randomized, sequential, international, multicentric, 2-arm, non-comparative, open-label, 2-stage clinical study to determine disease response rates therapy of Velcade™ in subjects who have relapsed or refractory follicular B-cell lymphoma (FLL).

Qualitative comparisons of the 2 treatment arms based on safety, efficacy and dosing convenience will be made in order to recommend a dose schedule for further clinical study.

It is anticipated that approximatively 120 subjects will be enrolled to achieve the required 110 evaluable subjects, 55 in each treatment arm. Patients who receive any amount of Velcade™ are evaluable. Subjects not evaluable for response will be replaced.

A central randomization will be used in this study. Subjects will be randomized and stratified with factors for prior therapies (1 or 2 versus > 2) and time to progression (TPP) for the last given anti-neoplastic therapy (≤ 12 months versus > 12 months).

The eligible subjects will be randomized to either Treatment Arm A or Treatment Arm B in a 1:1 ratio:

• Subjects randomized to Treatment Arm A will receive 1.5 mg/m² Velcade™ administered biweekly on Days 1, 4, 8, and 11 of a 21-day cycle. Patients will receive 8 cycles. The dose of Velcade™ received in schedule A will be 48 mg/m² over 24 weeks.
• Subjects randomized to Treatment Arm B will receive 1.6 mg/m² Velcade™ administered weekly on Days 1, 8, 15, and 22 of a 35-day cycle. Patients will receive 6 cycles. The dose of Velcade™ received in schedule B will be 38.4 mg/m² over 30 weeks.

Two additional cycles may be administered if the patient shows improvement to PR after 8 or 6 cycles for arm A or B, respectively.

Study drug dose and schedule reduction for toxicity will be allowed during the study.

A two stage interim analysis will be conducted in each treatment arm to determine whether either of the 2 treatments lacks sufficient efficacy.

The final analysis will be conducted when all subjects have had the opportunity to complete the 30 day post-treatment evaluation visit. All data from all visits up until this point will be used in the final analysis, including data from any follow-up visits that have occurred.

Patients will be recruited approximately over 2 years and followed until all data are available for final analysis.

The total duration of the study is expected to be 5 years.

Conditions

Follicular Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Arm A: a 21-day cycle of 1.5 mg/m2 Velcade™ twice weekly for 2 weeks. Days 1, 4, 8, and 11 of a 21-day cycle. Subjects in this treatment arm will receive a total of 8 cycles of treatment,

Group Type: ACTIVE_COMPARATOR

Bortezomib

Intervention Type: DRUG

Arm A: a 21-day cycle of 1.5 mg/m2 Velcade™ twice weekly for 2 weeks. Days 1, 4, 8, and 11 of a 21-day cycle

B

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Arm B: a 35-day cycle of 1.6 mg/m2 Velcade™once weekly for 4 weeks. Days 1, 8, 15, and 22 of a 35-day cycle. Subjects in this treatment arm will receive a total of 6 cycles of treatment, approximately 30 weeks.

Interventions

Bortezomib

Arm A: a 21-day cycle of 1.5 mg/m2 Velcade™ twice weekly for 2 weeks. Days 1, 4, 8, and 11 of a 21-day cycle

Intervention Type: DRUG

Bortezomib

Arm B: a 35-day cycle of 1.6 mg/m2 Velcade™once weekly for 4 weeks. Days 1, 8, 15, and 22 of a 35-day cycle. Subjects in this treatment arm will receive a total of 6 cycles of treatment, approximately 30 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female subject 18 years or older.
• Initial diagnosis of follicular B-cell lymphoma (CD20+) (grades 1, 2, and 3 based on the World Health Organization 1997 classification), in first or subsequent relapse or progression after prior anti-neoplastic treatment including previous rituximab treatment. Relapse or progression since previous anti-neoplastic therapy must be documented by new lesions or objective evidence of progression of existing lesions.
• At least 1 measurable lymph node mass that is >1.5 cm in 2 perpendicular dimensions, and has not been previously irradiated or has grown since previous irradiation.
• No active central nervous system (CNS) lymphoma
• Karnofsky Performance Status (KPS) >50% (Eastern Cooperative Oncology Group [ECOG] 0-2)
• The following laboratory values at screening, unless abnormalities are related to the lymphoma:

• Absolute neutrophil count (ANC) >1000 cells/dL;
• Platelets >50,000 cells/dL;
• Aspartate transaminase (AST) <3 x upper limit of normal (ULN);
• Alanine transaminase (ALT) <3 x ULN;
• Total bilirubin <2 x ULN;
• Creatinine level <150 µmol/L
• Toxic effects of previous therapy or surgery resolved to Grade 2 or better.
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. Women are neither breast feeding nor pregnant for the duration of the study. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. Male subject agrees to use an acceptable method of contraception for the duration of the study.
• Voluntary signed informed consent before performance of any study-related procedure not part of normal medical care.
• Patient with minimum life expectancy of 3 months.

Exclusion Criteria

• Any other type of lymphoma.
• Previous treatment with Velcade™.
• Anti-neoplastic or experimental or radiation therapy within 3 weeks before Day 1 of Cycle 1.
• Major surgery within 2 weeks before Day 1 of Cycle 1.
• Rituximab, alemtuzumab (Mabcampath®), or other unconjugated therapeutic antibody within 10 weeks before Day 1 of Cycle 1.
• Nitrosoureas within 6 weeks before Day 1 of Cycle 1.
• Radioimmunoconjugates or toxin immunoconjugates such as ibritumomab tiuxetan (Zevalin™), or tositumomab (Bexxar®) within 10 weeks before Day 1 of Cycle 1.
• Peripheral neuropathy or neuropathic pain of Grade 3 or worse.
• History of allergic reaction attributable to compounds containing boron or mannitol.
• Diagnosed or treated for a malignancy other than non-Hodgkin's lymphoma (NHL) within 5 years before Day 1 of Cycle 1, with the exception of complete resection of basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy.
• Active systemic infection requiring treatment.
• Previously known HIV positive serology.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Concurrent treatment with another investigational agent.
• Adult patient under guardian.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag International NV

INDUSTRY

Sponsor Role: collaborator

Lymphoma Study Association

OTHER

Sponsor Role: lead

Responsible Party

GELA

Principal Investigators

Bertrand Coiffier, MD

Role: STUDY_CHAIR

Hospices Civils de Lyon, Lyon, France

Vincent Ribrag, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Gustave Roussy, Villejuif, France

Locations

Groupe d'Etude des Lymphomes de l'adulte

Mont-Godinne, , Belgium

Service d'Hématologie - Centre Hospitalier Lyon-Sud

Pierre-Bénite, , France

Centre Henri Becquerel

Rouen, , France

Institut Gustave Roussy

Villejuif, , France

Countries

Belgium; France

References

O'Connor OA, Wright J, Moskowitz C, Muzzy J, MacGregor-Cortelli B, Stubblefield M, Straus D, Portlock C, Hamlin P, Choi E, Dumetrescu O, Esseltine D, Trehu E, Adams J, Schenkein D, Zelenetz AD. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2005 Feb 1;23(4):676-84. doi: 10.1200/JCO.2005.02.050. Epub 2004 Dec 21.

Reference Type: BACKGROUND

PMID: 15613699 (View on PubMed)

Goy A, Younes A, McLaughlin P, Pro B, Romaguera JE, Hagemeister F, Fayad L, Dang NH, Samaniego F, Wang M, Broglio K, Samuels B, Gilles F, Sarris AH, Hart S, Trehu E, Schenkein D, Cabanillas F, Rodriguez AM. Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2005 Feb 1;23(4):667-75. doi: 10.1200/JCO.2005.03.108. Epub 2004 Dec 21.

Reference Type: BACKGROUND

PMID: 15613697 (View on PubMed)

Related Links

http://www.gela.org

Official site of the Groupe d'Etudes des Lymphomes de l'Adulte (In french)

Other Identifiers

Janssen: 28866138-LYM-2003

Identifier Type: -

Identifier Source: secondary_id

Eudrac: 2005-000734-21

Identifier Type: -

Identifier Source: secondary_id

FL05-1

Identifier Type: -

Identifier Source: org_study_id