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

This study has been terminated.
(An arm closed due to lack of efficacy)
Sponsor:
Collaborator:
Janssen-Cilag International NV
Information provided by:
Lymphoma Study Association
ClinicalTrials.gov Identifier:
NCT00136591
First received: August 26, 2005
Last updated: October 22, 2010
Last verified: October 2010
  Purpose

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.


Condition Intervention Phase
Follicular Lymphoma
Drug: Bortezomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Velcade™ in Subjects With Relapsed or Refractory Follicular B-Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Lymphoma Study Association:

Primary Outcome Measures:
  • To determine the response rate to Velcade™ as a single agent [ Time Frame: End of treatment ]

Secondary Outcome Measures:
  • To determine the overall complete response (CR) rate (CR + complete response unconfirmed [CRu]) [ Time Frame: End of treatment ]
  • To determine time to progression (TTP) [ Time Frame: End of study ]
  • To determine overall survival [ Time Frame: End of study ]
  • To determine duration of response [ Time Frame: End of study ]
  • To determine the time to best response [ Time Frame: End of study ]
  • To evaluate the safety and tolerability of Velcade™ [ Time Frame: End of study ]
  • To evaluate the effects of Velcade™ given biweekly at 1.5 mg/m2 versus 1.6 mg/m2 weekly [ Time Frame: End of study ]

Enrollment: 87
Study Start Date: September 2005
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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,
Drug: 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
Experimental: B 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  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: NCT00136591

Locations
Belgium
Groupe d'Etude des Lymphomes de l'adulte
Mont-Godinne, Belgium
France
Service d'Hématologie - Centre Hospitalier Lyon-Sud
Pierre-Bénite cedex, France, 69495
Centre Henri Becquerel
Rouen, France, 76038
Institut Gustave Roussy
Villejuif, France
Sponsors and Collaborators
Lymphoma Study Association
Janssen-Cilag International NV
Investigators
Study Chair: Bertrand Coiffier, MD Hospices Civils de Lyon, Lyon, France
Principal Investigator: Vincent Ribrag, MD Institut Gustave Roussy, Villejuif, France
  More Information

Additional Information:
Publications:
Responsible Party: B Coiffier, GELA
ClinicalTrials.gov Identifier: NCT00136591     History of Changes
Other Study ID Numbers: FL05-1, Janssen: 28866138-LYM-2003, Eudrac: 2005-000734-21
Study First Received: August 26, 2005
Last Updated: October 22, 2010
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Lymphoma Study Association:
follicular lymphoma
bortezomib
relapse

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014