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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

Phase 3
18 Years
Open (Enrolling)
Follicular Lymphoma

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Trial Information

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

Radiotherapy is the only modality which has been proven to have curative potential in
patients with localised low grade lymphoma. Despite excellent control of the local tumour,
most patients relapse outside the area treated with radiation and most of these ultimately
die from lymphoma. This study tests the hypothesis that the addition of six cycles of
chemotherapy plus rituximab (systemic chemotherapy) can eradicate undetectable lymphoma
deposits outside the radiation field and thereby improve the cure rate. The study will
specifically test the hypothesis that six cycles of adjuvant CVP chemotherapy
(cyclophosphamide, vincristine, prednisolone) in combination with Rituximab will improve
progression-free survival for patients with stage I and II low-grade follicular lymphoma
treated with involved-field radiotherapy (IFRT). That is, will patients given radiotherapy
plus systemic chemotherapy live longer or remain free from disease longer than patients
treated with radiation alone? Radiotherapy alone is widely regarded as the standard
treatment for this disease.

There are a number of secondary endpoints to the study, as follows:

1. Comparison the pre- and post-treatment prevalence of the t(14:18) translocation, in
peripheral blood and bone marrow, of patients treated with either IFRT alone or IFRT
plus chemotherapy. This translocation is potentially a marker for minimal residual
disease and eradication of the marker from blood cells may have prognostic
implications. The clinical value of "molecular remission" as an early predictor of
freedom from progression (FFP) and survival will be assessed.

2. Comparison of overall survival and FFP for patients treated with IFRT alone with
overall survival and FFP for patients treated with combined IFRT and systemic therapy.
Delay of progression of disease may be of limited value if overall survival is the

3. Comparison of acute and late toxicity and second malignancy rates for patients treated
with IFRT or IFRT plus systemic therapy.

4. Delineation of the location of first relapse in relation to radiation therapy fields.

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression Free Survival.Period from the date of randomisation to 1st progression of disease or death from any cause.

Outcome Time Frame:

Main analysis when accrual is complete at approx. 10 years. Interim efficacy analysis at 5 years follow up. Updated analysis after 10 years of follow-up.

Safety Issue:


Principal Investigator

Michael MacManus, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Peter MacCallum Cancer Centre, Australia


Australia: Department of Health and Ageing Therapeutic Goods Administration

Study ID:

TROG 99.03



Start Date:

February 2000

Completion Date:

December 2022

Related Keywords:

  • Follicular Lymphoma
  • Radiotherapy
  • Chemotherapy
  • Rituximab
  • Randomised Trial
  • Stage I-II low grade follicular lymphoma
  • Lymphoma
  • Lymphoma, Follicular