Rituximab in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

• ClinicalTrials.gov Identifier: NCT00112931
• Recruitment Status: Completed
• First Posted: June 3, 2005
• Last Update Posted: May 9, 2024
• Sponsor: University College, London
• Collaborators: Cancer Research UK; Roche Pharma AG
• Information provided by (Responsible Party): University College, London

Tracking Information

• First Submitted Date: June 2, 2005
• First Posted Date: June 3, 2005
• Last Update Posted Date: May 9, 2024
• Study Start Date: September 2004
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 14, 2016): Time until initiation of therapy (chemotherapy or radiotherapy) [ Time Frame: Time from randomisation until the first day systemic chemotherapy or radiotherapy is given. If rituximab is given to patients in the watch and wait arm this will be considered as initiation of chemotherapy. ]
• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: November 14, 2016)

• Frequency of clinical spontaneous remission [ Time Frame: From randomisation until the initiation of chemotherapy in the watch and wait arm ]
• Cause specific survival [ Time Frame: Time from randomisation to death from lymphoma or immediate therapy related toxicity ]
• Overall survival [ Time Frame: Time from randomisation to death from any cause. ]
• Response rate at 25 months [ Time Frame: Response at 25 months ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Rituximab in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma
• Official Title: An Intergroup Randomised Trial of Rituximab Versus a Watch and Wait Strategy in Patients With Advanced Stage, Asymptomatic, Non-Bulky Follicular Lymphoma

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. It is not yet known whether rituximab is more effective than observation in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying rituximab to see how well it works compared to observation in treating patients with newly diagnosed stage II, stage III, or stage IV follicular non-Hodgkin's lymphoma with no symptoms.

Detailed Description

OBJECTIVES:

Primary

• Compare time to initiation of systemic chemotherapy or radiotherapy in patients with newly diagnosed, previously untreated, asymptomatic stage II-IV non-bulky follicular non-Hodgkin's lymphoma treated with rituximab vs observation only.

Secondary

• Compare the frequency of clinical spontaneous remission in patients treated with these regimens.
• Compare overall and cause-specific survival of patients treated with these regimens.
• Determine the effect of rituximab on complete and partial response in patients treated with subsequent systemic chemotherapy.
• Compare quality of life, in terms of functional well-being and anxiety and depression, of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, disease grade (1 vs 2 vs 3a), disease stage (II vs III vs IV), and age. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients undergo observation only until disease progression.
• Arm II: Patients receive induction rituximab IV on day 1. Treatment repeats weekly for up to 4 weeks.
• Arm III: Patients receive induction rituximab as in arm II. Patients then receive maintenance rituximab IV once on day 1 of weeks 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92, and 100.

In all arms, treatment continues in the absence of unacceptable toxicity or disease progression requiring systemic chemotherapy* or radiotherapy.

NOTE: *Rituximab administration in arm I is considered initiation of systemic chemotherapy

Quality of life is assessed at baseline (before and after randomization), every 2 months for 2 years, and then every 6 months for 2 years.

Patients are followed every 2 months for 2 years and then every 3 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 600 patients (200 per treatment arm) will be accrued for this study within 3 years.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma

Intervention

• Biological: rituximab
• Other: No treatment

Study Arms

• Active Comparator: Watch and Wait
  Watch and Wait - no treatment
  Intervention: Other: No treatment
• Experimental: Arm C Rituximab 4 and Rixuximab Maintenance
  4 infusions - 375mg/m2 every 2 months. A single dose of rituximab (375mg/m2 will then be given at 12, 20, 28, 36, 44, 52, 60, 68, 76, 84, 92 and 100 weeks
  Intervention: Biological: rituximab

• Publications *: Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, Warden J, Stevens L, Pocock CF, Miall F, Cunningham D, Davies J, Jack A, Stephens R, Walewski J, Ferhanoglu B, Bradstock K, Linch DC. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol. 2014 Apr;15(4):424-35. doi: 10.1016/S1470-2045(14)70027-0. Epub 2014 Mar 4.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 7, 2024): 462
• Original Enrollment: Not Provided
• Actual Study Completion Date: September 14, 2023
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed follicular non-Hodgkin's lymphoma

  • Diagnosed within the past 3 months
  • Grade 1, 2, or 3a disease
  • Stage II-IV disease
  • No evidence of histological transformation
• Bidimensionally measurable disease by clinical examination or radiography
• Asymptomatic disease without B symptoms or severe pruritus

• Low tumor burden, defined by all of the following criteria:

  • Lactic dehydrogenase normal
  • Largest nodal or extranodal mass < 7 cm
  • No more than 3 nodal sites with a diameter > 3 cm

  • No clinically detectable significant serous effusion by chest x-ray

    • Clinically non-evident small effusion on CT scan is not considered significant
  • Spleen enlargement ≤ 16 cm by CT scan
• Circulating tumor cells < 5,000/mm^3
• No organ compression (i.e., ureteric obstruction)

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,500/mm^3
• Platelet count > 100,000/mm^3
• Hemoglobin > 10 g/dL

Hepatic

• AST and ALT normal
• Alkaline phosphatase normal
• Bilirubin normal

Renal

• Creatinine < 2 times upper limit of normal (unless due to lymphoma)

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after completion of rituximab
• No known HIV positivity
• No other malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No critical organ failure
• No other immediate life-threatening disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No prior therapy for lymphoma

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, New Zealand, United Kingdom

Administrative Information

• NCT Number: NCT00112931
• Other Study ID Numbers: CDR0000427312; CRUK-2004-001621-16; EU-20509; ROCHE-CRUK-001621-16
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: University College, London
• Original Responsible Party: Not Provided
• Current Study Sponsor: University College, London
• Original Study Sponsor: Cancer Research UK

Collaborators

• Cancer Research UK
• Roche Pharma AG

Investigators

• Study Chair: Kirit Ardeshna; Mount Vernon Cancer Centre at Mount Vernon Hospital

• PRS Account: University College, London
• Verification Date: May 2024