Condition category
Cancer
Date applied
17/09/2008
Date assigned
25/09/2008
Last edited
16/05/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Peter Hillmen

ORCID ID

Contact details

Department of Haematology
Level 3
Bexley Wing
St. James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
+44 (0)113 206 8513
peter.hillmen@nhs.net

Additional identifiers

EudraCT number

2009-010998-20

ClinicalTrials.gov number

Protocol/serial number

HTA 07/01/38; Sponsor ref: HM09/8848

Study information

Scientific title

A randomised, phase IIB trial in previously untreated patients with chronic lymphocytic leukaemia (CLL) to compare fludarabine, cyclophosphamide and rituximab (FCR) with FC, mitoxantrone and low dose rituximab (FCM-miniR)

Acronym

ARCTIC

Study hypothesis

This trial aims to establish whether the addition of mitoxantrone (M) with a reduced dose of rituximab (R), to fludarabine (F) and cyclophosphamide (C) - FCM-miniR is as effective as FCR in terms of response in patients with previously untreated chronic lymphocytic leukaemia (CLL).

Please note that the target number of participants has been updated from 200 to 206 as of 19/02/2009.

Please note that the public title was added to this ISRCTN record as of 20/02/2009.

Please note that, as of 11/05/2009, the anticipated start and end dates have been updated from 01/03/2009 and 01/05/2011 to 01/01/2009 and 31/12/2011, respectively.

Ethics approval

Leeds (East) Research Ethics Committee on 25/06/2009 (ref: 09/H1306/54)

Study design

Multi-centre phase II open non-inferiority randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Chronic lymphocytic leukaemia (CLL)

Intervention

Patients will be randomised to receive 6 cycles of either FCR or FCM-miniR according to the following regimens:

Fludarabine, cyclophosphamide and rituximab (FCR):

Fludarabine (oral)* 24 mg/m^2/day, Days 1 to 5
Cyclophosphamide (oral)* 150 mg/m^2/day, Days 1 to 5
Rituximab (intravenous) 375 mg/m^2, Day 1 (Cycle 1)
Rituximab (intravenous) 500 mg/m^2, Day 1 (Cycle 2-6)

Cycles of FCR are repeated every 28 days for a total of 6 cycles.

G-CSF (lenograstim 263 mg/day) for days 7 to 13 is recommended for all subsequent cycles in patients who have to have a previous dose delay due to neutropenia.

*Patients should be questioned regarding nausea and vomiting or diarrhoea occurring with the prior cycle of therapy and if this is present then the fludarabine and cyclophosphamide should be given via the intravenous route due to concerns over drug absorption. Intravenous fludarabine (25 mg/m^2/day for 3 days) and cyclophosphamide (250mg/m2/day for 3 days) regimens are recommended if the oral regimen is not tolerated.


Fludarabine, cyclophosphamide, rituximab and mitoxantrone (FCM-miniR):

Fludarabine (oral)* 24 mg/m^2/day, Days 1 to 5
Cyclophosphamide (oral)* 150 mg/m^2/day, Days 1 to 5
Mitoxantrone (intravenous) 6 mg/m^2/day, Day 1
Mini Rituximab (intravenous) 100 mg, Day 1

Cycles of FCM-miniR are repeated every 28 days for a total of 6 cycles.

G-CSF (lenograstim 263 mg/day) for days 7 to 13 is recommended for all subsequent cycles in patients who have to have a previous dose delay due to neutropenia.

*Patients should be questioned regarding nausea and vomiting or diarrhoea occurring with the prior cycle of therapy and if this is present then the fludarabine and cyclophosphamide should be given via the intravenous route due to concerns over drug absorption. Intravenous fludarabine (25 mg/m^2/day for 3 days) and cyclophosphamide (250 mg/m^2/day for 3 days) regimens are recommended if the oral regimen is not tolerated.

Patients will be evaluated every 6 months after the end of therapy until disease progression requiring therapy or until 2 years post-randomisation. All patients will be followed-up for survival until death as part of a long term follow-up registry which is currently in set-up.

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measures

Proportion of patients achieving a complete response (CR), as defined by the IWCLL criteria. A formal assessment of response by IWCLL criteria will be made 3 months after the end of therapy.

Secondary outcome measures

1. Proportion of patients with undetectable minimal residual disease (MRD) according to the IWCLL Response Criteria, assessed at baseline and 3 months after the end of therapy. Patients who are MRD negative at the end of treatment will also be followed up every 6 months after the end of therapy until disease progression requiring therapy or 2 years post-randomisation. All patients will be followed up for survival until death.
2. Overall response rate defined as complete or partial remission by IWCLL Criteria at 3 months after the end of therapy
3. Progression-free survival at 2 years
4. Overall survival at 2 years
5. Safety and toxicity. Adverse events (AEs) related to the treatment will be collected from randomisation until 30 days after the last dose of treatment with FCR or FCM-miniR.
6. Economic evaluation (time frame not yet finalised)

Overall trial start date

01/01/2009

Overall trial end date

31/12/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Both males and females, at least 18 years old
2. B-CLL with a characteristic immunophenotype
3. Binet's Stages B, C or Progressive Stage A
4. Requiring therapy by the International Workshop on CLL (IWCLL) criteria in that they must have at least one of the following: Evidence of progressive marrow failure as manifested by the development of, or worsening of, anaemia and/or thrombocytopenia
5. Massive (i.e. 6 cm below the left costal margin) or progressive or symptomatic splenomegaly
6. Massive nodes (i.e. 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
7. Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time (LDT) of less than 6 months as long as the lymphocyte count is over 30 x 10^9/L
8. A minimum of any one of the following disease-related symptoms must be present:
8.1. Unintentional weight loss more than or equal to 10% within the previous 6 months
8.2. Significant fatigue (i.e. Eastern Cooperative Oncology Group PS 2 or worse; cannot work or unable to perform usual activities)
8.3. Fevers of greater than 38.0°C for 2 or more weeks without other evidence of infection
8.4. Night sweats for more than 1 month without evidence of infection
9. No prior therapy for CLL
10. World Health Organization (WHO) performance status (PS) of 0, 1 or 2
11. Able to provide written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

206

Participant exclusion criteria

1. Prior therapy for CLL
2. Active infection
3. Past history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanised monoclonal antibodies
4. Pregnancy, lactation or women of child-bearing potential unwilling to use medically approved contraception whilst receiving treatment
5. Men whose partners are capable of having children but who are not willing to use appropriate medically approved contraception during the study, unless they are surgically sterile
6. Central nervous system (CNS) involvement with CLL
7. Mantle cell lymphoma
8. Other severe, concurrent diseases or mental disorders
9. Known HIV positive
10. Patient has active or prior hepatitis B or C
11. Active secondary malignancy excluding basal cell carcinoma
12. Persisting severe pancytopenia (neutrophils <0.5 x 10^9/l or platelets <50 x 10^9/l) or transfusion dependent anaemia unless due to direct marrow infiltration by CLL
13. Active haemolysis (patients with haemolysis controlled with prednisolone at a dose 10 mg or less per day can be entered into the trial)
14. Patients with a creatinine clearance of less than 30 ml/min (either measured or derived by the Cockcroft formula)

Recruitment start date

01/01/2009

Recruitment end date

31/12/2011

Locations

Countries of recruitment

Ireland, United Kingdom

Trial participating centre

Department of Haematology
Leeds
LS9 7TF
United Kingdom

Sponsor information

Organisation

Leeds Teaching Hospitals NHS Trust (UK)

Sponsor details

Research & Development
Floor A/B - Old Site
Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
United Kingdom
derek.norfolk@leedsth.nhs.uk

Sponsor type

Government

Website

http://www.leedsteachinghospitals.com

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment Programme - HTA (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes