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Trial registered on ANZCTR


Registration number
ACTRN12608000404325
Ethics application status
Approved
Date submitted
25/07/2008
Date registered
18/08/2008
Date last updated
18/09/2023
Date data sharing statement initially provided
8/02/2021
Date results provided
8/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
An Australian, phase II , multicentre, randomised, open-label, dose intensification study of three patient cohorts, investigating varying dose schedules, each of 6 x 28day cycles, with monitoring continuing for 12 months into the post treatment period.
Scientific title
An Australian, phase II , multicentre, randomised, dose intensification study investigating oral fludarabine, oral cyclophosphamide, and intravenous rituximab (poFCivR) tolerance in previously untreated elderly (=65years old) patients with chronic lymphocytic leukaemia. (CLL)
Secondary ID [1] 650 0
Australasian Leukaemia and Lymphoma Group: ALLG CLL5
Secondary ID [2] 661 0
Australasian Leukaemia and Lymphoma Group
Universal Trial Number (UTN)
Trial acronym
OFOCIR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukaemia (CLL) 3462 0
Chronic Lymphocytic Leukaemia (CLL) 3503 0
Condition category
Condition code
Cancer 3623 3623 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
To investigate the safety and tolerability of fludarabine, cyclophosphamide, and rituximab in previously untreated elderly (=65years old) patients with chronic lymphocytic leukaemia. (CLL).
Treatment Arm1:oral fludarabine 24 mg/m2 days 1-5. plus intravenous (i.v.) rituximab Cycle 1: 375 mg/m2 day 0*
Cycles 2-6: 500 mg/m2 day 1 (Fludarabine Rituximab:FR5),
Treatment Arm2 and Arm3 :oral fludarabine 24 mg/m2 days 1-3. plus oral cyclophosphamide 150 mg/m2 days 1-3. in varing dose intensity with i.v. rituximab Cycle 1: 375 mg/m2 day 0*
Cycles 2-6: 500 mg/m2 day 1 (Fludarabine Cyclophosphamide Rituximab: FCR3 and Fludarabine Cyclophosphamide Rituximab FCR 5).
Dose schedule is determined via randomisation.
Duration is x6 28day cycles.
There is no wash out period between cycles.
Intervention code [1] 3192 0
Treatment: Drugs
Comparator / control treatment
'There are three cohorts of active treatment. Randomisation arms allocated via randomisation (as described in the description of the interventions)'.
Control group
Dose comparison

Outcomes
Primary outcome [1] 4518 0
The proportion of patients completing 6 treatment cycles
Timepoint [1] 4518 0
24 weeks (6 x 28 day cycles)
Secondary outcome [1] 7638 0
Rate of grade 4 haematological toxicities, as defined by National Cancer Institute Common Toxicity Criteria NCI-CTC Grading Scale for haematological toxicity for patients in this study. Documented in Protocol.
Timepoint [1] 7638 0
14 month follow-up (final staging 2 months post-treatment + 12 months follow-up)
Secondary outcome [2] 7639 0
Rate of grade 3+ non-haematological toxicities as defined by NCI-CTC Grading Scale for haematological toxicity for patients in this study. Documented in Protocol.
Timepoint [2] 7639 0
14 month follow-up (final staging 2 months post-treatment + 12 months follow-up)
Secondary outcome [3] 7640 0
Overall response rate (ORR), Complete Response (CR), Complete Remission with incomplete marrow recovery (CRi), Nodular Partial Remission (nPR), Partial Remission (PR).
Timepoint [3] 7640 0
14 month follow-up (final staging 2 months post-treatment + 12 months follow-up)
Secondary outcome [4] 7641 0
Quality of Life (QoL)
European Organisation for Research and Treatment of Cancer EORTC QLQ-C30 questionnaire Version3.
Timepoint [4] 7641 0
14 month follow-up (final staging 2 months post-treatment + 12 months follow-up)
Secondary outcome [5] 7642 0
The proportion of responding patients at the end of the follow-up period. Those responding to treatment at the end of treatment.
Timepoint [5] 7642 0
14 month follow-up (final staging 2 months post-treatment + 12 months follow-up)
Secondary outcome [6] 7643 0
Progression-free survival (PFS), overall survival (OS)
Timepoint [6] 7643 0
14 month follow-up (final staging 2 months post-treatment + 12 months follow-up)
Secondary outcome [7] 7644 0
Rate of treatment-related adverse events
Timepoint [7] 7644 0
14 month follow-up (final staging 2 months post-treatment + 12 months follow-up)

Eligibility
Key inclusion criteria
1. B-CLL confirmed according to National Cancer Institute (NCI) Working Group Criteria.
2. Binet stage B or C, or progressive symptomatic stage A (see Protocol Appendix I).
3. Age = 65 years old.
4. Judged to be in need of systemic therapy (see Protocol Appendix II).
5. No previous treatment (chemotherapy, radiotherapy or immunotherapy) for CLL.
6. Alkaline phosphatase and transaminases = 2 x ULN.(Upper Limits of Normal)
7. Creatinine clearance = 50 ml/min (as calculated by (estimated Glomerular Filtration Rate) eGFR; eGFR also calculated by
Cockcroft and Gault formula for final analysis; see Protocol Appendix III).
8. Females of childbearing potential or fertile males must take contraceptive measures during
and at least 6 months after cessation of therapy.
9. (Eastern Cooperative Group) ECOG performance status 0-1.
10. Cumulative Illnes Rating Scale CIRS score < 6 (see Protocol Appendix IV).
11. Life expectancy > 6 months.
12. Patient’s written informed consent.
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Age < 65 years old.
2. Non-progressive or stable Binet stage A.
3. Clinically significant auto-immune cytopenia, Coombs-positive haemolytic anaemia (as
discerned by treating physician).
4. Active second malignancy currently requiring treatment (except for non-melanoma skin
cancer or cervical cancer in situ or tumour treated curatively by surgery > 5 years ago)
5. Concomitant disease requiring prolonged use of glucocorticoids (> 1 month).
6. Known hypersensitivity with anaphylactic reaction to humanised monoclonal antibodies or
any of the study drugs.
7. ECOG performance status 2-3.
8. Class III or IV cardiac disease defined by the NYHA.
9. Severe or debilitating pulmonary disease.
10. Severe or debilitating central nervous system disease or cerebral dysfunction.
11. Transformation to aggressive B-cell malignancy, e.g. diffuse large cell lymphoma, Richter’s
syndrome or prolymphocytic leukaemia.
12. Active bacterial, viral or fungal infection; patients who have known Human Immunodeficiency
Virus (HIV) infection or active hepatitis B virus (HBV) or hepatitis C virus
(HCV) infection.
13. Total bilirubin > 2 x ULN.
14. Creatinine clearance < 50 ml/min (as calculated by eGFR).
15. Any coexisting medical or psychological condition that would preclude participation in the
required study procedures.
16. Treatment with any other investigational agent, or participation in another clinical trial
within 30 days prior to entering this study.
17. Pregnancy and lactation.

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)
central randomisation by phone /fax /computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomization table created by a computer software (i.e., computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/08/2008
Actual
10/12/2008
Date of last participant enrolment
Anticipated
Actual
31/05/2010
Date of last data collection
Anticipated
31/05/2018
Actual
31/05/2018
Sample size
Target
120
Accrual to date
Final
120
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,SA,WA,NT,TAS
Recruitment hospital [1] 8123 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 8124 0
Border Medical Oncology - Albury
Recruitment hospital [3] 8125 0
The Canberra Hospital - Garran
Recruitment hospital [4] 8126 0
Coffs Harbour Base Hospital - Coffs Harbour
Recruitment hospital [5] 8127 0
Concord Repatriation Hospital - Concord
Recruitment hospital [6] 8128 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [7] 8129 0
Frankston Hospital - Frankston
Recruitment hospital [8] 8130 0
Gold Coast Hospital - Southport
Recruitment hospital [9] 8131 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [10] 8132 0
Gosford Hospital - Gosford
Recruitment hospital [11] 8133 0
Royal Hobart Hospital - Hobart
Recruitment hospital [12] 8134 0
Launceston General Hospital - Launceston
Recruitment hospital [13] 8135 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [14] 8136 0
Mater Misericordiae Hospital Bundaberg - Bundaberg
Recruitment hospital [15] 8137 0
Port Macquarie Private Hospital - Port Macquarie
Recruitment hospital [16] 8138 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [17] 8139 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [18] 8140 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [19] 8141 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [20] 8142 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [21] 8143 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [22] 8144 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [23] 8145 0
St George Hospital - Kogarah
Recruitment hospital [24] 8146 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [25] 8147 0
Westmead Hospital - Westmead
Recruitment hospital [26] 8148 0
Wollongong Hospital - Wollongong
Recruitment postcode(s) [1] 16184 0
3084 - Heidelberg
Recruitment postcode(s) [2] 16185 0
3690 - Wodonga
Recruitment postcode(s) [3] 16186 0
2605 - Garran
Recruitment postcode(s) [4] 16187 0
2450 - Coffs Harbour
Recruitment postcode(s) [5] 16188 0
2139 - Concord
Recruitment postcode(s) [6] 16189 0
5042 - Bedford Park
Recruitment postcode(s) [7] 16190 0
3199 - Frankston
Recruitment postcode(s) [8] 16191 0
4215 - Southport
Recruitment postcode(s) [9] 16192 0
3220 - Geelong
Recruitment postcode(s) [10] 16193 0
2250 - Gosford
Recruitment postcode(s) [11] 16194 0
7000 - Hobart
Recruitment postcode(s) [12] 16195 0
7250 - Launceston
Recruitment postcode(s) [13] 16196 0
3168 - Clayton
Recruitment postcode(s) [14] 16197 0
4670 - Bundaberg
Recruitment postcode(s) [15] 16198 0
2444 - Port Macquarie
Recruitment postcode(s) [16] 16199 0
4102 - Woolloongabba
Recruitment postcode(s) [17] 16200 0
3000 - Melbourne
Recruitment postcode(s) [18] 16201 0
5011 - Woodville
Recruitment postcode(s) [19] 16202 0
0810 - Tiwi
Recruitment postcode(s) [20] 16203 0
3050 - Parkville
Recruitment postcode(s) [21] 16204 0
2065 - St Leonards
Recruitment postcode(s) [22] 16205 0
6009 - Nedlands
Recruitment postcode(s) [23] 16206 0
2217 - Kogarah
Recruitment postcode(s) [24] 16207 0
3065 - Fitzroy
Recruitment postcode(s) [25] 16208 0
2145 - Westmead
Recruitment postcode(s) [26] 16209 0
2500 - Wollongong

Funding & Sponsors
Funding source category [1] 3645 0
Commercial sector/Industry
Name [1] 3645 0
Roche
Country [1] 3645 0
Australia
Funding source category [2] 3646 0
Commercial sector/Industry
Name [2] 3646 0
Bayer
Country [2] 3646 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
Level 2, 10 St Andrews Place, East Melbourne 3001 Victoria
Country
Australia
Secondary sponsor category [1] 3277 0
None
Name [1] 3277 0
Address [1] 3277 0
Country [1] 3277 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297793 0
Northern Sydney Central Coast Health
Ethics committee address [1] 297793 0
Ethics committee country [1] 297793 0
Australia
Date submitted for ethics approval [1] 297793 0
18/06/2008
Approval date [1] 297793 0
19/09/2008
Ethics approval number [1] 297793 0

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

Contacts
Principal investigator
Name 28782 0
Prof Stephen Mulligan
Address 28782 0
Department of Haematology, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065U
Country 28782 0
Australia
Phone 28782 0
0299267601
Fax 28782 0
Email 28782 0
mulligan@staff.usyd.edu.au
Contact person for public queries
Name 11939 0
Stephen Mulligan
Address 11939 0
Department of Haematology, Royal North Shore Hospital. St Leonards, Sydney. NSW 2065
Country 11939 0
Australia
Phone 11939 0
02-9926 7601
Fax 11939 0
02-9906 1635
Email 11939 0
mulligan@staff.usyd.edu.au
Contact person for scientific queries
Name 2867 0
Stephen Mulligan
Address 2867 0
Department of Haematology, Royal North Shore Hospital. St Leonards, Sydney. NSW 2065
Country 2867 0
Australia
Phone 2867 0
02-9926 7601
Fax 2867 0
02-9906 1635
Email 2867 0
mulligan@staff.usyd.edu.au

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
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
19913Study 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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