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Follicular LymphomaPhase 3NCT00115700

Radiotherapy Versus Radiotherapy Plus Chemotherapy in Early Stage Follicular Lymphoma

A Phase 3 study testing Cyclophosphamide, Radiotherapy and Vincristine in people with Follicular Lymphoma, run by Trans Tasman Radiation Oncology Group at 21 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Follicular Lymphoma
What is being tested?
Cyclophosphamide, Radiotherapy and Vincristine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
21 sitesin 3 countries
Study dates
Feb 2000to Aug 2018
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 9Show fewer
  • 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.

Trial locations and contacts

21 sites in 3 countries.

21 sites in 3 countries

Australia17 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • St John of God Hospital

    Ballarat, Victoria, 3350

  • Peter MacCallum Cancer Centre

    East Melbourne, Victoria, 3002

  • The Canberra Hospital

    Garran, Australian Capital Territory, 2605

  • Andrew Love Cancer Care Centre, Geelong Hospital

    Geelong, Victoria, 3220

  • Austin Health

    Heidelberg, Victoria, 3084

  • Launceston General Hospital

    Launceston, Tasmania, 7250

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • Calvary Mater Newcastle

    Newcastle, New South Wales, 2298

  • Prince of Wales Hospital

    Randwick, New South Wales, 2031

  • Radiation Oncology - Mater Centre

    South Brisbane, Queensland, 4101

  • Genesis Cancer Care (previously Premion)

    Tugun, Queensland, 4224

  • Westmead Hospital

    Wentworthville, New South Wales, 2145

  • Albury Base/Murray Valley Private Hospital

    West Albury, New South Wales, 2640

  • Illawarra Cancer Care Centre

    Wollongong, New South Wales, 2500

  • The Queen Elizabeth Hospital

    Woodville, South Australia, 5011

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

New Zealand3 sites

  • Auckland Hospital

    Auckland, 1001

  • Waikato Hospital

    Hamilton, 3200

  • Wellington Hospital

    Wellington, 7902

Other trials in New Zealand

Canada1 site

  • Princess Margaret Hospital

    Toronto

Other trials in Canada

About this study

Official title: 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

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.

Read the detailed description

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 same.
  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.
Being tested
Cyclophosphamide, Radiotherapy, Vincristine, Prednisolone, Rituximab
Keywords
Radiotherapy, Chemotherapy, Rituximab, Randomised Trial, Stage I-II low grade follicular lymphoma
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called Cycloblastin, Endoxan

    1000 mg/m2 I.V. on day 1

  • RadiotherapyRadiation

    Also called Radiation

    The prescribed dose to the target volume will be 30 Gy. Daily fractions of 1.5-2.0 Gy will be employed.

  • VincristineDrug

    Also called Vincristine Sulfate Injection

    1.4 mg/m2 (maximum single dose of 2 mg) I.V. on day 1

  • PrednisoloneDrug

    Also called Panafcort, Panafcortelone, Predsone, Predsolone

    50 mg/m2 orally daily for days 1 - 5

  • RituximabDrug

    Also called Erbitux, Mabthera

    375 mg/m2 IV Infusion day 1

Study groups in NCT00115700
Study groupRoleWhat they receive
Radiotherapy+ ChemotherapyExperimentalInvolved field Radiotherapy (RT) 30-36 GY plus Cyclophosphamide, Vincristine and Prednisolone (CVP) + rituximab × 6 cycles
Receives: Drug: Cyclophosphamide; Radiation: Radiotherapy; Drug: Vincristine; Drug: Prednisolone; Drug: Rituximab
Radiotherapy aloneActive comparatorInvolved field Radiotherapy (30-36 GY) alone
Receives: Radiation: Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 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)

  1. Pre- and post-treatment prevalence of the t(14;18) translocation, in peripheral blood and bone marrow between arms

    Measured: 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

  2. Overall Survival (OS)

    Period from date of randomisation to date of death from any cause.

    Measured: 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

  3. Location of first relapse

    Period from date of randomisation to date of first relapse location via CT scan and or other imaging as required

    Measured: 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

  4. To compare time to evolution to higher histological grade

    Period from date of randomisation to date of higher histological grade via CT scan and or other imaging as required

    Measured: 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

  5. Freedom from progression.

    Period from date of randomisation to date of first disease progression.

    Measured: 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

  6. Acute and late toxicities and secondary malignances

    Measured: Frame 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jun 2005 (estimated)
  2. Study startFeb 2000
  3. Primary completionAug 2018
  4. Study completionAug 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
150 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00115700
Sponsor's protocol ID
TROG 99.03
Other IDs
ALLG NHLLOW5
Status last verified
Nov 2022
First submitted
23 Jun 2005
Last updated
18 Nov 2022
Results posted
No
Data monitoring committee
No

Publications

  • Johnstone P, Bressel M, Seymour JF, Juneja S, Ahmad H, MacManus M. Secondary outcomes of the TROG 99.03 randomized trial of systemic therapy after involved-field radiotherapy in early-stage follicular lymphoma, including toxicity, relapse and second malignancy data. Radiother Oncol. 2026 Apr;217:111388. doi: 10.1016/j.radonc.2026.111388. Epub 2026 Jan 22.

    PubMed 41580147

  • 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.

    PubMed 29975623

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cyclophosphamide, Radiotherapy and Vincristine in people with Follicular Lymphoma, run by Trans Tasman Radiation Oncology Group at 21 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Australia, New Zealand, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS). Period from the date of randomisation to 1st progression of disease or death from any cause. (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00115700, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2022.

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