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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
St Andrews Place, East Melbourne, Victoria 3002
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
This study evaluated the effectiveness of high dose Cyclophosphamide, Epirubicin, Vincristine and Prednisolone ifosfamide (CEOP) chemotherapy regime with Filgrastim, and standard dose CEOP chemotherapy regime in patients with non-Hodgkin's lymphoma (NHL).
Who was it for?
Patients were eligible to join this study if they were aged 16 years or more, had been diagnosed with NHL (Histological types: Follicular large cell (Group D), Diffuse mixed small cleaved and large cell (Group F), Diffuse large cell (Group G) or Large cell immunoblastic (Group H)), and had not received previous chemotherapy or radiation therapy for NHL.
Trial details
Participants in this trial were randomly (by chance) allocated to one of two treatment groups. Participants in group 1 received a high dose CEOP chemotherapy regime with Filgrastim which involved 1500mg/m2 of Cyclophosphamide intravenously on day 1, 150 mg/m2 of Epirubicin intravenously on day 1, 1.4 mg/m2 (maximum of 2.0mg) of Vincristine intravenously on day 1, 100 mg/day of Prednisolone orally from days 1 to 5, and 5 micrograms/kg/day of Filgrastim subcutaneously from day 2 until Absolute Neutrophil Count was greater than 10 x 109/L for a maximum of 14 days. This treatment regime was repeated every 3 weeks and was administered to participants 6 times. Participants in group 2 received standard dose CEOP which included 750mg/m2 of Cyclophosphamide intravenously on day 1, 75mg/m2 of Epirubicin intravenously on day 1, 1.4mg/m2 (maximum of 2.0 mg) of Vincristine intravenously on day 1, and 100 mg/day of Prednisolone orally from days 1 to 5. Similarly to group 1, this treatment regime was repeated every 3 weeks and was administered to participants 6 times.
All participants were assessed prior to treatment, after 3 courses of the treatment, at completion of the 6 courses of the treatment, at 3 months post treatment, at 6 months post treatment and at 5 years post treatment to assess the effectiveness of the treatment regimes.
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
[email protected]
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
[email protected]
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
[email protected]

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 [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
20190Study protocol  [email protected] Access can be requested via the Health Data Austra... [More Details]



Results publications and other study-related documents

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