Radiotherapy Versus Radiotherapy Plus Chemotherapy in Early Stage Follicular Lymphoma

NCT ID: NCT00115700

Last Updated: 2022-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-02-29
• Study Completion Date: 2018-08-31

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.

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.

Conditions

Follicular Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Radiotherapy+ Chemotherapy

Involved field Radiotherapy (RT) 30-36 GY plus Cyclophosphamide, Vincristine and Prednisolone (CVP) + rituximab × 6 cycles

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

1000 mg/m2 I.V. on day 1

Radiotherapy

Intervention Type: RADIATION

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

Vincristine

Intervention Type: DRUG

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

Prednisolone

Intervention Type: DRUG

50 mg/m2 orally daily for days 1 - 5

Rituximab

Intervention Type: DRUG

375 mg/m2 IV Infusion day 1

Radiotherapy alone

Involved field Radiotherapy (30-36 GY) alone

Group Type: ACTIVE_COMPARATOR

Radiotherapy

Intervention Type: RADIATION

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

Interventions

Cyclophosphamide

1000 mg/m2 I.V. on day 1

Intervention Type: DRUG

Radiotherapy

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

Intervention Type: RADIATION

Vincristine

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

Intervention Type: DRUG

Prednisolone

50 mg/m2 orally daily for days 1 - 5

Intervention Type: DRUG

Rituximab

375 mg/m2 IV Infusion day 1

Intervention Type: DRUG

Other Intervention Names

Cycloblastin, Endoxan; Radiation; Vincristine Sulfate Injection; Panafcort, Panafcortelone, Predsone, Predsolone; Erbitux, Mabthera

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Australasian Leukaemia and Lymphoma Group

OTHER

Sponsor Role: collaborator

Trans Tasman Radiation Oncology Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael MacManus, MD

Role: STUDY_CHAIR

Peter MacCallum Cancer Centre, Australia

Locations

The Canberra Hospital

Garran, Australian Capital Territory, Australia

Calvary Mater Newcastle

Newcastle, New South Wales, Australia

Prince of Wales Hospital

Randwick, New South Wales, Australia

Westmead Hospital

Wentworthville, New South Wales, Australia

Albury Base/Murray Valley Private Hospital

West Albury, New South Wales, Australia

Illawarra Cancer Care Centre

Wollongong, New South Wales, Australia

Radiation Oncology - Mater Centre

South Brisbane, Queensland, Australia

Genesis Cancer Care (previously Premion)

Tugun, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

The Queen Elizabeth Hospital

Woodville, South Australia, Australia

Launceston General Hospital

Launceston, Tasmania, Australia

St John of God Hospital

Ballarat, Victoria, Australia

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

Andrew Love Cancer Care Centre, Geelong Hospital

Geelong, Victoria, Australia

Austin Health

Heidelberg, Victoria, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Princess Margaret Hospital

Toronto, , Canada

Auckland Hospital

Auckland, , New Zealand

Waikato Hospital

Hamilton, , New Zealand

Wellington Hospital

Wellington, , New Zealand

Countries

Australia; Canada; New Zealand

References

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.

Reference Type: DERIVED

PMID: 29975623 (View on PubMed)

Related Links

http://www.trog.com.au

Click here for more information about this study on the TROG official website

Other Identifiers

ALLG NHLLOW5

Identifier Type: OTHER

Identifier Source: secondary_id

TROG 99.03

Identifier Type: -

Identifier Source: org_study_id