Radiotherapy Versus Radiotherapy Plus Chemotherapy in Early Stage Follicular Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Australasian Leukaemia and Lymphoma Group
Information provided by (Responsible Party):
Trans-Tasman Radiation Oncology Group (TROG)
ClinicalTrials.gov Identifier:
NCT00115700
First received: June 23, 2005
Last updated: August 6, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Follicular Lymphoma
Drug: Cyclophosphamide
Radiation: Radiotherapy
Drug: Vincristine
Drug: Prednisolone
Drug: Rituximab
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Trans-Tasman Radiation Oncology Group (TROG):

Primary Outcome Measures:
  • Progression Free Survival.Period from the date of randomisation to 1st progression of disease or death from any cause. [ 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pre- and post-treatment prevalence of the t(14;18) translocation, in peripheral blood and bone marrow between arms [ Time Frame: Peripheral blood should be analysed by PCR at commencment of treatment, after 1 year and upon relapse. ] [ Designated as safety issue: No ]
  • Overall Survival. Period from date of randomisation to date of death from any cause. [ Time Frame: Main analysis when accrual is complete at approx. 10 years. Updated analysis after 10 years of follow-up. ] [ Designated as safety issue: No ]
  • Location of first relapse. [ Time Frame: The numbers of infield and all relapses will be confidentially reviewed every 6 months until the end of accrual by an independent reviewer. Main analysis when accrual is complete at approx. 10 years. Updated analysis after 10 years of follow-up. ] [ Designated as safety issue: No ]
  • To compare time to evolution to higher histological grade [ Time Frame: Main analysis when accrual is complete at approx. 10 years. Updated analysis after 10 years of follow-up. ] [ Designated as safety issue: No ]
  • Freedom from progression. Period from date of randomisation to date of first disease progression. [ Time Frame: Main analysis when accrual is complete at approx. 10 years. Updated analysis after 10 years of follow-up. ] [ Designated as safety issue: No ]
  • Acute and late toxicities. [ Time Frame: An interim analysis of acute toxicity once all patients in the first cohort have finished their treatment and have been followed for 3 mths. Main analysis when accrual is complete at approx. 10 yrs. Updated after 10 yrs of follow-up. ] [ Designated as safety issue: Yes ]

Enrollment: 150
Study Start Date: February 2000
Estimated Study Completion Date: December 2022
Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Radiotherapy+ Chemotherapy
Involved field Radiotherapy (RT) 30-36 GY plus Cyclophosphamide, Vincristine and Prednisolone (CVP) + rituximab × 6 cycles
Drug: Cyclophosphamide
1000 mg/m2 I.V. on day 1
Other Name: Cycloblastin, Endoxan
Radiation: Radiotherapy
The prescribed dose to the target volume will be 30 Gy. Daily fractions of 1.5-2.0 Gy will be employed.
Other Name: Radiation
Drug: Vincristine
1.4 mg/m2 (maximum single dose of 2 mg) I.V. on day 1
Other Name: Vincristine Sulfate Injection
Drug: Prednisolone
50 mg/m2 orally daily for days 1 - 5
Other Name: Panafcort, Panafcortelone, Predsone, Predsolone
Drug: Rituximab
375 mg/m2 IV Infusion day 1
Other Name: Erbitux, Mabthera
Active Comparator: Radiotherapy alone
Involved field Radiotherapy (30-36 GY) alone
Radiation: Radiotherapy
The prescribed dose to the target volume will be 30 Gy. Daily fractions of 1.5-2.0 Gy will be employed.
Other Name: Radiation

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00115700

Locations
Australia, Australian Capital Territory
The Canberra Hospital
Garran, Australian Capital Territory, Australia, 2605
Australia, New South Wales
Calvary Mater Newcastle
Newcastle, New South Wales, Australia, 2298
Prince of Wales Hospital
Randwick, New South Wales, Australia, 2031
Westmead Hospital
Wentworthville, New South Wales, Australia, 2145
Illawarra Cancer Care Centre
Wollongong, New South Wales, Australia, 2500
Australia, Queensland
Radiation Oncology - Mater Centre
South Brisbane, Queensland, Australia, 4101
Premion - Tugun
Tugun, Queensland, Australia, 4224
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
The Queen Elizabeth Hospital
Woodville, South Australia, Australia, 5011
Australia, Tasmania
Launceston General Hospital
Launceston, Tasmania, Australia, 7250
Australia, Victoria
St John of God Hospital
Ballarat, Victoria, Australia, 3350
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
Andrew Love Cancer Care Centre, Geelong Hospital
Geelong, Victoria, Australia, 3220
Austin Health
Heidelberg, Victoria, Australia, 3084
Murray Valley Private Hospital
Wodonga, Victoria, Australia, 3690
Australia, Western Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
Canada
Princess Margaret Hospital
Toronto, Canada
New Zealand
Auckland Hospital
Auckland, New Zealand, 1001
Waikato Hospital
Hamilton, New Zealand, 3200
Wellington Hospital
Wellington, New Zealand, 7902
Sponsors and Collaborators
Trans-Tasman Radiation Oncology Group (TROG)
Australasian Leukaemia and Lymphoma Group
Investigators
Study Chair: Michael MacManus, MD Peter MacCallum Cancer Centre, Australia
  More Information

Additional Information:
No publications provided

Responsible Party: Trans-Tasman Radiation Oncology Group (TROG)
ClinicalTrials.gov Identifier: NCT00115700     History of Changes
Other Study ID Numbers: TROG 99.03, ALLG NHLLOW5
Study First Received: June 23, 2005
Last Updated: August 6, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Trans-Tasman Radiation Oncology Group (TROG):
Radiotherapy
Chemotherapy
Rituximab
Randomised Trial
Stage I-II low grade follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Prednisolone
Methylprednisolone Hemisuccinate
Vincristine
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on April 22, 2014