Radiotherapy Versus Radiotherapy Plus Chemotherapy in Early Stage Follicular Lymphoma
A Randomised Multicentre Trial of Involved Field Radiotherapy Versus Involved Field Radiotherapy Plus Chemotherapy in Combination With Rituximab (Mabthera®) for Stage I - II Low Grade Follicular Lymphoma
2 other identifiers
interventional
150
3 countries
21
Brief Summary
Patients with stage I and II low grade follicular lymphoma are randomised between standard therapy (involved field radiotherapy) and investigational therapy (involved field radiotherapy and chemotherapy plus rituximab). The main endpoint is progression free survival but overall survival and the influence of t(14;18) status will also be studied.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Feb 2000
Longer than P75 for phase_3
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2000
CompletedFirst Submitted
Initial submission to the registry
June 23, 2005
CompletedFirst Posted
Study publicly available on registry
June 24, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 2018
CompletedNovember 18, 2022
November 1, 2022
18.5 years
June 23, 2005
November 16, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS). Period from the date of randomisation to 1st progression of disease or death from any cause.
Main analysis after at least 3 years of follow-up following the end of accrual. An updated analysis may be done on completion of 5 years follow-up after the end of accrual. Long term follow-up analysis is planned after 10 years of follow-up
Secondary Outcomes (6)
Pre- and post-treatment prevalence of the t(14;18) translocation, in peripheral blood and bone marrow between arms
Peripheral blood at commencement of treatment, after 1 year and upon relapse is collected and stored for later analysis to be done as part of translational studies when funding becomes available
Overall Survival (OS)
Main analysis will be done on completion of 5 years follow-up after the end of accrual. An interim analysis to be done after at least 3 years of follow-up. A futility analysis will be performed after the 5 year analysis. In the absence of futility being
Location of first relapse
Main analysis after at least 3 years of follow-up following the end of accrual. An updated analysis may be done on completion of 5 years follow-up after the end of accrual
To compare time to evolution to higher histological grade
Main analysis after at least 3 years of follow-up following the end of accrual. An updated analysis may be done on completion of 5 years follow-up after the end of accrual
Freedom from progression.
Main analysis after at least 3 years of follow-up following the end of accrual. An updated analysis may be done on completion of 5 years follow-up after the end of accrual. Long term follow-up analysis is planned after 10 years of follow-up
- +1 more secondary outcomes
Study Arms (2)
Radiotherapy+ Chemotherapy
EXPERIMENTALInvolved field Radiotherapy (RT) 30-36 GY plus Cyclophosphamide, Vincristine and Prednisolone (CVP) + rituximab × 6 cycles
Radiotherapy alone
ACTIVE COMPARATORInvolved field Radiotherapy (30-36 GY) alone
Interventions
1000 mg/m2 I.V. on day 1
The prescribed dose to the target volume will be 30 Gy. Daily fractions of 1.5-2.0 Gy will be employed.
1.4 mg/m2 (maximum single dose of 2 mg) I.V. on day 1
50 mg/m2 orally daily for days 1 - 5
Eligibility Criteria
You may qualify if:
- Adult patients (≥ 18 years old) with histologically documented "follicular lymphoma, grade 1", grade 2", or "follicular lymphoma, grade 3a" diagnosed following an excisional, incisional or generous core biopsy. (i.e. an FNA alone is insufficient.)
- Disease limited to stages I and II after adequate staging
- Anticipated life expectancy \> 5 years
- Given written informed consent
- Been assessed by a radiation oncologist and a medical oncologist/ haematologist
- WCC \> 3.0 x 10\^9/L, platelet count \> 100 x 10\^9/L, serum creatinine \< 0.15 mmol/L
- Ability to commence radiotherapy within 6 weeks of randomisation
- Women using effective contraception, are not pregnant and agree not to become pregnant during participating in the trial and during the 12 months thereafter. Men agree not to father a child during participation in the trial and during the 12 months thereafter.
You may not qualify if:
- Received previous systemic cytotoxic chemotherapy.
- Received previous radiotherapy, (except superficial radiation therapy for non-melanoma skin cancers).
- Received previous immunotherapy.
- A medical contraindication to radiotherapy, chemotherapy, or rituximab.
- Any previous or concurrent malignancy other than curatively treated non-melanoma skin cancer, level 1 malignant melanoma, or in situ cervical cancer, unless disease and treatment-free for 5 years.
- Such extensive involvement of the thorax that treatment with radiation therapy alone would be hazardous because of excessive lung irradiation, even if a shrinking field technique were employed.
- Suspected or confirmed pregnancy. Must not be lactating.
- Patients who have known human immuno-deficiency virus (HIV) infection or active hepatitis B (HBV).
- Treatment within a clinical study within 30 days prior to study entry.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
The Canberra Hospital
Garran, Australian Capital Territory, 2605, Australia
Calvary Mater Newcastle
Newcastle, New South Wales, 2298, Australia
Prince of Wales Hospital
Randwick, New South Wales, 2031, Australia
Westmead Hospital
Wentworthville, New South Wales, 2145, Australia
Albury Base/Murray Valley Private Hospital
West Albury, New South Wales, 2640, Australia
Illawarra Cancer Care Centre
Wollongong, New South Wales, 2500, Australia
Radiation Oncology - Mater Centre
South Brisbane, Queensland, 4101, Australia
Genesis Cancer Care (previously Premion)
Tugun, Queensland, 4224, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
The Queen Elizabeth Hospital
Woodville, South Australia, 5011, Australia
Launceston General Hospital
Launceston, Tasmania, 7250, Australia
St John of God Hospital
Ballarat, Victoria, 3350, Australia
Peter MacCallum Cancer Centre
East Melbourne, Victoria, 3002, Australia
Andrew Love Cancer Care Centre, Geelong Hospital
Geelong, Victoria, 3220, Australia
Austin Health
Heidelberg, Victoria, 3084, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009, Australia
Princess Margaret Hospital
Toronto, Canada
Auckland Hospital
Auckland, 1001, New Zealand
Waikato Hospital
Hamilton, 3200, New Zealand
Wellington Hospital
Wellington, 7902, New Zealand
Related Publications (1)
MacManus M, Fisher R, Roos D, O'Brien P, Macann A, Davis S, Tsang R, Christie D, McClure B, Joseph D, Jayamohan J, Seymour JF. Randomized Trial of Systemic Therapy After Involved-Field Radiotherapy in Patients With Early-Stage Follicular Lymphoma: TROG 99.03. J Clin Oncol. 2018 Oct 10;36(29):2918-2925. doi: 10.1200/JCO.2018.77.9892. Epub 2018 Jul 5.
PMID: 29975623DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Michael MacManus, MD
Peter MacCallum Cancer Centre, Australia
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 23, 2005
First Posted
June 24, 2005
Study Start
February 1, 2000
Primary Completion
August 1, 2018
Study Completion
August 1, 2018
Last Updated
November 18, 2022
Record last verified: 2022-11