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Trial registered on ANZCTR


Registration number
ACTRN12613000909729
Ethics application status
Approved
Date submitted
4/06/2013
Date registered
14/08/2013
Date last updated
31/08/2023
Date data sharing statement initially provided
31/08/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Phase III randomised trial of high dose Cyclophosphamide, Epirubicin, Vincristine and Prednisolone (CEOP) chemotherapy regimen & Filgrastim versus standard dose CEOP chemotherapy regimen in patients with non-Hodgkin’s lymphoma
Scientific title
Phase III randomised trial of high dose Cyclophosphamide, Epirubicin, Vincristine and Prednisolone (CEOP) chemotherapy regimen & Filgrastim versus standard dose CEOP chemotherapy regimen in patients with non-Hodgkin’s lymphoma
Secondary ID [1] 282424 0
nil
Universal Trial Number (UTN)
U1111-1142-5062
Trial acronym
ALLG NHL07
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin Lymphoma 289021 0
Condition category
Condition code
Cancer 289360 289360 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
HIGH DOSE CEOP. One cycle consisted of:
Cyclophosphamide 1500mg/m2 intravenously Day 1
Epirubicin 150mg/m2 intravenously Day 1
Vincristine (max 2.0 mg) 1.4 mg/m2 intravenouslyDay 1
Prednisolone 100mg/D orally Days 1-5
Filgrastim 5 microg/kg/D subcutaneously Days 2 until absolute neutrophil count (ANC) >10X 109/L (max. 14 days)
The above regimen was repeated every 3 weeks for 6 to 8 cycles depending on when the patient achieved complete response (CR). Patients were then assessed 3 months following completion of treatment and then at the clinician's discretion or upon request from the Trial Centre. All patients were followed up for a minimum of 10 years.
Intervention code [1] 287061 0
Treatment: Drugs
Comparator / control treatment
STANDARD DOSE CEOP. One cycle consisted of
Cyclophosphamide 750mg/m2 intravenously Day 1
Epirubicin 75mg/m2 intravenously Day 1
Vincristine (max 2.0 mg) 1.4 mg/m2 intravenously Day 1
Prednisolone 100mg/D orally Days 1-5
The above regimen was repeated every 3 weeks for 6 to 8 cycles depending on when the patient achieved complete response (CR). Patients were then assessed 3 months following completion of treatment and then at the clinician's discretion or upon request from the Trial Centre. All patients were followed up for a minimum of 10 years.
Control group
Active

Outcomes
Primary outcome [1] 289512 0
The primary endpoint was overall survival (OS) 5 years after randomisation, analysed by intention-to-treat analysis including all eligible randomised patients. The reverse Kaplan-Meier method was used to calculate the estimated median duration of follow-up. OS was measured from the date of randomisation, to the date of death (no matter what the cause). Survival proportions were estimated using the Kaplan-Meier product-limit method. Hazard ratios (HR) were estimated using the Cox proportional hazards model, stratified by the International Prognostic Index (IPI), including a stratum for patients with unknown IPI.
Timepoint [1] 289512 0
5 years post treatment
Secondary outcome [1] 302661 0
Quality of life (QoL) was measured using the European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C308 version 1 questionnaire and scored accordingly. Quality of life scores were compared using t-tests.
Timepoint [1] 302661 0
Baseline, after 3 courses, after 6 courses (completion of treatment), after 3 months, after 6 months
Secondary outcome [2] 302662 0
Response rate. Response rates were compared using an exact test for stratified 2x2 tables, with strata based on the International Prognostic Index (IPI).
Timepoint [2] 302662 0
After 3 months of treatment
Secondary outcome [3] 304062 0
Progression-free survival (PFS) 5 years after randomisation, analysed by intention-to-treat analysis including all eligible randomised patients. Survival proportions were estimated using the Kaplan-Meier product-limit method. Hazard ratios (HR) were estimated using the Cox proportional hazards model, stratified by the IPI, including a stratum for patients with unknown IPI.
Timepoint [3] 304062 0
5 years
Secondary outcome [4] 304063 0
Time to progression 5 years after randomisation, analysed by intention-to-treat analysis including all eligible randomised patients. Survival proportions were estimated using the Kaplan-Meier product-limit method. Hazard ratios (HR) were estimated using the Cox proportional hazards model, stratified by the IPI, including a stratum for patients with unknown IPI.
Timepoint [4] 304063 0
5 years
Secondary outcome [5] 304143 0
Toxicity was analysed by intention-to-treat analysis including all eligible randomised patients. . Toxicity grades were compared using the exact version of the Wilcoxon-Mann-Whitney test comparing two ordered multinomial distributions and the incidence of grade 3 or 4 toxicities and other binary endpoints were compared using Fisher’s exact test. Non-censored continuous variables were compared using the exact version of the Wilcoxon-Mann-Whitney test.
Timepoint [5] 304143 0
Toxicity was recorded at the end of each cycle and for 30 days following the last cycle of treatment.

Eligibility
Key inclusion criteria
1. Patients with non-Hodgkin’s lymphoma of the following histological types:
-Follicular large cell (Group D).
-Diffuse mixed small cleaved and large cell (Group F).
-Diffuse large cell (Group G).
-Large cell immunoblastic (Group H).
2. Ann Arbor Stage I with bulky disease (tumour mass >=10cm in largest diameter), II, III or IV.
3. Age >=16 years.
4. Measurable or evaluable disease.
5. Absolute neutrophil count >1.5 x 109/L, platelet count >75 x 109/L, unless cytopenia is due to bone marrow infiltration.
6. Adequate renal function (creatinine less than twice upper limit of normal); adequate hepatic function (bilirubin less than twice upper limit of normal).
7. ECOG performance status 0-3.
8. Accessible for treatment and follow-up.
9. Informed consent in accordance with institutional ethical guidelines.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1 Previous chemotherapy or radiation therapy for lymphoma. Use of corticosteroids alone does not make patient ineligible.
2 A known contra-indication to any of the trial drugs.
3 Past or current malignancies at other sites, except adequately treated squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix.
4 Congestive cardiac failure or symptomatic coronary artery disease. Patients with other pre-existing cardiac disease may be entered at the investigator’s discretion provided cardiac investigations are satisfactory (ECG and LVEF).
5 Patients who are pregnant or breast feeding or women of child bearing age who are not taking adequate contraceptive precautions.
6 Patients with primary CNS lymphoma.
7 Known HIV antibody positive.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
The trial had a target sample size of 250 eligible patients. It was calculated that it would enable an increase in the five-year survival proportion from 35% to 55% to be detected with a probability (power) of 0.83 or an increase from 35% to 60% to be detected with probability 0.93 using a 2-tailed test of significance at significance level (alpha) = 0.05 assuming 90% of patients were followed for at least 5 years.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
3/03/1994
Actual
3/03/1994
Date of last participant enrolment
Anticipated
Actual
25/03/1999
Date of last data collection
Anticipated
Actual
27/09/2016
Sample size
Target
250
Accrual to date
Final
250
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 5054 0
New Zealand
State/province [1] 5054 0

Funding & Sponsors
Funding source category [1] 287195 0
Commercial sector/Industry
Name [1] 287195 0
Pharmacia Pty Ltd
now Pfizer Australia
Country [1] 287195 0
Australia
Funding source category [2] 287196 0
Commercial sector/Industry
Name [2] 287196 0
Amgen Australia Pty Ltd
Country [2] 287196 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
Level 5, 10 St Andrews Place, East Melbourne, Victoria 3002, Australia
Country
Australia
Secondary sponsor category [1] 285959 0
None
Name [1] 285959 0
Address [1] 285959 0
Country [1] 285959 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289189 0
Peter MacCallum Cancer Centre
Ethics committee address [1] 289189 0
Ethics committee country [1] 289189 0
Australia
Date submitted for ethics approval [1] 289189 0
Approval date [1] 289189 0
07/12/1993
Ethics approval number [1] 289189 0
93/21

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 39690 0
A/Prof Max Wolf
Address 39690 0
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002
Country 39690 0
Australia
Phone 39690 0
+613 9656 1111
Fax 39690 0
Email 39690 0
max.wolf@petermac.org
Contact person for public queries
Name 39691 0
Max Wolf
Address 39691 0
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002
Country 39691 0
Australia
Phone 39691 0
+613 9656 1111
Fax 39691 0
Email 39691 0
max.wolf@petermac.org
Contact person for scientific queries
Name 39692 0
Max Wolf
Address 39692 0
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002
Country 39692 0
Australia
Phone 39692 0
+613 9656 9013
Fax 39692 0
Email 39692 0
max.wolf@petermac.org

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified IPD data for all data collected during the trial
When will data be available (start and end dates)?
Data available 3 months following publication, for an indefinite period
Available to whom?
Data are potentially available to:
• Researchers from not-for-profit organisations
• Commercial organisations
• Other
Based in:
• Any location
Further information:
All data requests will be considered by the primary sponsor on a case by case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement (or similar) that the requester must agree to before access is granted.
Available for what types of analyses?
Any type of analysis
Proposals will be assessed on a case-by-case basis
How or where can data be obtained?
Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health/). Search for the ACTRN number in the catalogue to find datasets associated with this trial or email enquiries to info@allg.org.au


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
20190Study protocol  info@allg.org.au Access can be requested via the Health Data Austra... [More Details]



Results publications and other study-related documents

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