The first prospective, randomized trial of cell culture drug resistance testing (CCDRT) is currently taking place in the United Kingdom (UK). It is part of a large trial in which 750 newly-diagnosed patients are being enrolled. The first goal of the study is simply a very traditional three-arm trial to compare three different forms of empiric chemotherapy in newly-diagnosed CLL. Patients are randomized to treatment with chlorambucil (Untreated Arm I), Fludarabine (Untreated Arm II), or Fludarabine + Cyclophosphamide (Untreated Arm III). Most CLL patients ultimately relapse (or have primary refractory disease) following first line therapy. Relapsing/refractory patients are then re-randomized to receive either CCDRT-directed chemotherapy (Refractory/Relapsed Arm I) or "standard," empiric therapy (Refractory/Relapsed Arm II).
Study details are described on the following web site and are excerpted below:
http://www.clinicaltrials.gov/ct/show/NCT00004218?order=1
Official Title: Phase III Randomized Study of Chlorambucil Alone Versus Fludarabine With or Without Cyclophosphamide in Patients With Newly Diagnosed Chronic Lymphocytic Leukemia
Study chair/Principal investigator
Daniel Catovsky, MD, Study Chair, Royal Marsden NHS Trust
Sponsored by
Leukemia Research Fund
Medical Research Council
Further Study Details:
OBJECTIVES:
1. - Compare the survival
rate of patients with newly diagnosed chronic lymphocytic leukemia treated
with chlorambucil alone vs fludarabine with or without cyclophosphamide.
2. - Compare the response
rate and duration of remission in patients treated with these regimens.
3. - Compare the toxic
effects of these regimens in these patients.
4. - Compare the quality
of life of patients treated with these regimens.
5. - Determine the impact of the drug response information provided by the DiSC assay on response rate and survival in relapsed or nonresponding patients.
6. - Assess the prognostic value of five genetic markers: trisomy 12 and deletions at 11q23, 13q14, p53, and 6q21 in patients treated with these regimens.
OUTLINE: This is a randomized study. Patients enter one of three treatment arms in the first randomization. Depending on response, some patients may also participate in a second randomization to one of two treatment arms.
Untreated Arm I: Patients receive oral chlorambucil daily for 7 days. Treatment repeats every 4 weeks until maximum response or up to 1 year.
Untreated Arm II: Patients receive fludarabine IV or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses.
Untreated Arm III: Patients receive cyclophosphamide IV and fludarabine IV for 3 days or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses. Patients who relapse after being in remission for at least 1 year may repeat the initial therapy or may participate in a second randomization. Patients who experience progressive disease or relapse within 1 year after treatment proceed to a second randomization.
Relapsed/Refractory Arm I: Treatment is guided by the results of the DiSC assay. Treatment may be one of the first-line treatments with fludarabine or standard CHOP chemotherapy repeated every 4 weeks (cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisolone on days 1-5) or any other therapy guided by the results of the DiSC assay.
Relapsed/Refractory Arm II: Treatment is physician's choice, which may include any of the options in arm I. Quality of life is assessed prior to initial therapy; at 3, 6, and 12 months; and then annually thereafter.
Patients are followed annually for survival.
PROJECTED ACCRUAL: A total of 750 patients will be accrued for this
study within 6-7 years.
Location and Contact Information
Argentina
Hospital
Alvarez, Buenos Aires, Argentina; Recruiting
R F Bezares, MD
54-11-4612-3480
Hospital
Italiano de Buenos Aires, Buenos Aires, CP1181ACH, Argentina;
Recruiting
D. Fantl, MD
54-11-4958-2463 dorotea.fantl@hospitalitaliano.org.ar
Croatia
University
Hospital Rebro, Zagreb, 10000, Croatia; Recruiting
I. Radman, MD
385-1-238-8277 iradman@inet.hr
Greece
University
of Ioannina, Ioannina, GR-45110, Greece; Recruiting
K. L. Bouzantas, MD
32-2510-24974
University
of Patras Medical School, Rio Patras, GR-26500, Greece; Recruiting
N Giannakoulas, MD
30-061-999-247 ngiannakoulas@hotmail.com
Ireland
Galway
University Hospital, Galway, Ireland; Recruiting
M Murray, MD
353-91-524-222
St. James's
Hospital, Dublin, 8, Ireland; Recruiting
Shaun R. McCann, MD
353-1416-2169
Italy
Ospedali
Riuniti di Bergamo, Bergamo, 24100, Italy; Recruiting
A Grassi, MD
39-035-269-859 ext. 931
New Zealand
Canterbury
Health Laboratories, Christchurch, New Zealand; Recruiting
P. Ganly, PhD, FRCP,
FRCPath, FRCPA 64-3-3641450 peter.ganly@cdhb.govt.nz
Russian Federation
Russian
Academy of Medical Sciences Cancer Research Center, Moscow, 115478,
Russian Federation; Recruiting
M A Volkova, MD
095-324-23-24
United Kingdom, England
Addenbrooke's
NHS Trust, Cambridge, England, CB2 2QQ, United Kingdom;
Recruiting
Robert Marcus, MD
44-1223-217-071
Aintree
University Hospital, Liverpool, England, L9 7AL, United
Kingdom; Recruiting
W Sadik, MD
44-151-525-5980
Ashford
Hospital, Ashford, England, TW15 3AA, United Kingdom;
Recruiting
A. S. Laurie, MD
44-1784-884-488
Bassetlaw
Hospital & Community Services NHS Trust, Nottinghamshire, England,
S81 3SA, United
Kingdom; Recruiting
B Paul, MD 44-1909-50-0990
beverley.paul@dbh.nhs.uk
Birmingham
Heartlands and Solihull NHS Trust -Teaching, Birmingham, England,
B9 5SS, United
Kingdom; Recruiting
D.W. Milligan, MD
44-0121-424-2000 ext. 43703 an d.w.milligan@bham.ac.uk
Bishop
Auckland Hospital, Durham, England, United Kingdom; Recruiting
G P Galvin, MD
44-1388-604-040
Blackpool
Victoria Hospital, Blackpool, England, FY3 8NR, United
Kingdom; Recruiting
P R Kelsey, MD
44-20-7210-4850
Bradford
Hospitals NHS Trust, Bradford, England, BD9 6RJ, United
Kingdom; Recruiting
J Newton, MD
44-1274-542-200
Cancer
Care Center at York Hospital, York, England, Y031 8HE,
United Kingdom; Recruiting
L. R. Bond, MD
44-1904-725-854 Lee.Bond@york.uk
Chesterfield
Royal Hospital, Chesterfield, England, S44 5BL, United
Kingdom; Recruiting
R Stewart, MD
44-1246-552-567
City Hospital
- Birmingham, Birmingham, England, B18 7QH, United Kingdom;
Recruiting
D. Bareford, MD
44-121-507-4234 d.bareford@bham.ac.uk
Conquest
Hospital, Saint Leonards-on-Sea, England, TN37 7RD, United
Kingdom; Recruiting
J Beard, MD
44-1424-755-255
Countess
of Chester Hospital, Chester, England, CH2 1UL, United
Kingdom; Recruiting
Elisabeth Rhodes,
MD 44-1244-365-000
Darlington
Memorial, Darlington, England, DL3 6HX, United Kingdom;
Recruiting
P J Williamson, MD
44-1325-74-3222
Dartford
& Gravesham NHS Trust, Joyce Green Hospital, Dartford Kent, England,
DA1 5PL, United
Kingdom; Recruiting
Vivienne E. Andrews,
MD 44-1322-227-242
Doncaster
Royal Infirmary, Doncaster, England, DN2 5LT, United
Kingdom; Recruiting
Gautam Majumdar, MD,
FRCP, FRCPath 44-130-236-6666 gautam.majumdar@dbh.nhs.uk
Epsom General
Hospital, Epsom Surrey, England, KT18 7E9, United Kingdom;
Recruiting
Lydia Jones, MD, BSc,
BS, FRCP, FRCPath 44-1372-735-735 lydia.jones@epsom-sthelier.nhs.uk
Farnborough
Hospital, Orpington Kent, England, BR6 8ND, United Kingdom;
Recruiting
C F M De Lord, MD
44-168-981-4100
Gloucester
Royal NHS Trust - Glouchester Royal Hospital, Gloucester, England,
GL1 3NN, United
Kingdom; Recruiting
J Ropner, MD
44-1452-528-555
Good Hope
Hospital Trust, West Midlands, England, B75 7RR, United
Kingdom; Recruiting
Malcolm S. Hamilton,
MD 0121-378-2211 ext. 2202 malcolm.hamilton@goodhope.nhs.uk
Guy's and
St. Thomas' Hospitals NHS Trust, London, England, SE1 9RT,
United Kingdom; Recruiting
Stephen Schey, MD
44-207-955-5000
Harrogate
District Hospital, Harrogate, England, HG2 7SX, United
Kingdom; Recruiting
A. G. Bynoe, MD
01423-885959
Hemel Hempstead
General, Hemel Hempstead, England, United Kingdom; Recruiting
J F M Harrison, MD
44-1442-213-141
Horton
Hospital, Banbury, England, OX16 9A, United Kingdom;
Recruiting
Jill Durrant, MB,
FRCPath 44-1865-404-863 jilldurrant@doctors.org.uk
Huddersfield
Royal Infirmary, Huddersfield, West Yorks, England, HD3 3EA,
United Kingdom; Recruiting
C. Carter, MD, MBCHB,
FRCP, FRCP (EDIN), 44-1484-422-191
Hull Royal
Infirmary, Hull, England, HU3 2KZ, United Kingdom; Recruiting
R.L. Shields, MD
44-1482-674-542
Institute
of Oncology and Radiology of Serbia, High Wycombe, England,
United Kingdom; Recruiting
R. Aitchison, MD
+44-1494 425224
Leeds General
Infirmary at Leeds Teaching Hospital NHS Trust, Leeds, England,
LS1 3EX, United
Kingdom; Recruiting
J.A. Child, MD
0-113 392 51 53 tonych@ulth.northy.nhs.uk
Leicester
Royal Infirmary, Leicester, England, LE1 5WW, United
Kingdom; Recruiting
M.J. Dyer, MD
44-116-252-3222 mjsd1@le.ac.uk
North Hampshire
Hospital, Basingstoke, England, RG24 9NA, United Kingdom;
Recruiting
A E Milne, MBBS, F,R,CP
44-1256-31-4793
North Staffs
Royal Infirmary, Stoke on Trent, England, ST4 7LN, United
Kingdom; Recruiting
P M Chipping, MD
44-1782-62-2463
Northampton
General Hospital NHS Trust, Northampton, England, NN1 5BD,
United Kingdom; Recruiting
J R Y Ross, MD
44-1604-63-4700
Northern
Cancer Network, Newcastle upon Tyne, England, NE7 7DN,
United Kingdom; Recruiting
J P Wallis, MD
44-191-223-1313
Nottingham
City Hospital NHS Trust, Nottingham, England, NG5 1PB,
United Kingdom; Recruiting
Andy Haynes, MD
0115-9691169 ext. 46704 andy.haynes@nottingham.ac.uk
Oldchurch
Hospital, Romford, England, RM7 OBE, United Kingdom;
Recruiting
Alison Brownell, MD
44-0170-345-533
Pontefract
General Infirmary, Pontefract West Yorkshire, England, WF8
1PL, United Kingdom; Recruiting
D. Wright, MD
44-1977-600-600
Queen Elizabeth
Hospital, Gateshead, England, NE9 6SX, United Kingdom;
Recruiting
Alex M. Hendrick,
MD
Queen Elizabeth
Hospital, Gateshead-Tyne and Wear, England, NE9 6SX,
United Kingdom; Recruiting
G.P. Summerfield,
DM, FRCP, FRCPPath 0191-403-2878
Rotherham
District General Hospital - NHS Trust, Rotherham, England,
S60 2UD, United Kingdom; Recruiting
Helen Barker, MD
44-1709-820-000
Royal Berkshire
Hospital, Reading, England, RG1 5AN, United Kingdom;
Recruiting
H Grech, MD
44-118-987-5111
Royal Bournemouth
Hospital, Bournemouth, England, BH7 7DW, United Kingdom;
Recruiting
David Graham Oscier,
MD 1-20-270-4790 david.oscier@lineone.net
Royal Free
Hospital, London, England, NW3 2QG, United Kingdom; Recruiting
A B Mehta, MD
44-171-794-0500
Royal Liverpool
and Broadgreen Hospitals, Liverpool, England, L7 8XP,
United Kingdom; Recruiting
P Chu, MD 44-151-706-2000
Royal Marsden
NHS Trust - London, London, England, SW3 6JJ, United
Kingdom; Recruiting
Daniel Catovsky, MD
44-20-7808-2880 ext.2875 daniel.catovsky@icr.ac.uk
Royal South
Hants Hospital, Southampton, England, SO14 0YG, United
Kingdom; Recruiting
A. Duncombe, MD
44-23-8063-4288
Royal Surrey
County Hospital, Guildford, England, GU2 5XX, United
Kingdom; Recruiting
G Robbins, MD
01483-464122
Royal Sussex
County Hospital, Brighton, England, BN2 5BE, United Kingdom;
Recruiting
J Duncan, MD
01273-664658 john.duncan@brighton-healthcare.nhs.uk
Russells
Hall Hospital, Dudley, England, DY1 2HQ, United Kingdom;
Recruiting
P Harrison, MB, FRCP,
MRCPath 01384 456111
Saint Richards
Hospital, Chichester, England, P019 4SE, United Kingdom;
Recruiting
P. Stross, MD
44-1243-788-122
Scunthorpe
General Hospital, Scunthorpe, England, DN15 7BH, United
Kingdom; Recruiting
S. Jalihal, MD
44-1724-282-282 Sanjeev.Jalihal@nlg.nhs.uk
Selly Oak
Hospital at University Hospital NHS Trust, Birmingham, England,
B29 6JD, United Kingdom; Recruiting
J A Murray, MD
44-121-627-1627 ext. 53709 jim.murray@university-b.wmids.nhs.uk
Southampton
General Hospital, Southampton, England, SO16 6YD, United
Kingdom; Recruiting
K Orchard, MD
440-238-079-4118 kho@soton.ac.uk
St Helier
Hospital, Carshalton, England, SM5 1AA, United Kingdom;
Recruiting
J Mercieca, MD
44-20-8296-2972
St. George's
Hospital, London, England, SW17 0QT, United Kingdom;
Recruiting
C E Dearden, MD
020-8725-5446
Staffordshire
General Hospital, Stafford, England, ST16 3SA, United
Kingdom; Recruiting
P. Revell, MD
44-1785-257-731 jayne.anslow@msgh-tr.wmids.nhs.uk
Stoke Mandeville
Hospital, Aylesbury-Buckinghamshire, England, HP21 8AL,
United Kingdom; Recruiting
A Watson, MD
44-1296-315-000
Torbay
Hospital, Torquay Devon, England, TQ2 7AA, United Kingdom;
Recruiting
S.R. Smith, MD
44-1803-65-5237
Walton
General Hospital, Liverpool, England, L9 1AE, United
Kingdom; Recruiting
P.A. Stevenson, MD,
FACP, MB, ChB 44-151-525-3611
West Middlesex
Hospital, Middlesex, England, N18 1QZ, United Kingdom;
Recruiting
M. Sekhar, MD
44-208-565-5716 mallika.sekhar@wmuh-tr.nthames.nhs.uk
Wharfdale
General Hospital, Otley, England, LS21 7AA, United Kingdom;
Recruiting
G M Smith, MD
39-44-1943-465-522
Whipps
Cross Hospital, London, England, E11 1NR, United Kingdom;
Recruiting
C. Desilva, MD
44-20-8539-5522
Worthing
Hospital, Worthing, England, BN11 2DH, United Kingdom;
Recruiting
C. L. Rist, MD
44-1903-205-111 COLIN.RIST@WASH-TR.STHAMES.NHS.UK
United Kingdom, Northern Ireland
Belfast
City Hospital Trust, Belfast, Northern Ireland, BT9 7AB,
United Kingdom; Recruiting
R.J.G. Cuthbert, MD,
FRCP, FRCPath 44-28-9032-9241 robert.cuthbert@bll.n.i.nhs.uk
Craigavon
Area Hospital, Portadown, Craigavon, Northern Ireland, BT63
5QQ, United Kingdom; Recruiting
C. Humphrey, MD
028-38-612651
Ulster
Hospital, Dundonald, Northern Ireland, BT16, United Kingdom;
Recruiting
M El-Agnaf, MD
44-2-890-48-4511
United Kingdom, Scotland
Aberdeen
Royal Infirmary, Aberdeen, Scotland, AB25 2ZN, United
Kingdom; Recruiting
Dominic J. Culligan,
MD 44-1224-553-394 dominic.culligan@arh.grampian.scot.nhs.uk
Dumfries
Royal Infirmary, Dumfries, Scotland, DG1 4AP, United
Kingdom; Recruiting
R K B Dang, MD
44-1387-241-441 r.dang@dgri.scot.nhs.uk
Raigmore
Hospital, Inverness, Scotland, 1V2 3UJ, United Kingdom;
Recruiting
C J Lush, MD
463-704258 chris.lush@raigmore.scot.nhs.uk
Royal Alexandra
Hospital, Paisley, Scotland, United Kingdom; Recruiting
Pamela Mckay, MD
44-141-580-4225
Southern
General Hospital, Glasgow, Scotland, G51 4TF, United
Kingdom; Recruiting
A E Morrison, MD
44-141-201-1100
Victoria
Hospital, Kirkcaldy, Scotland, KY2 5AH, United Kingdom;
Recruiting
C J Mccallum, MD
44-1592-643-355
Western
General Hospital, Edinburgh, Scotland, EH4 2XU, United
Kingdom; Recruiting
P R E Johnson, MD
0131-537-2595 peter.johnson@luht.scot.nhs.uk
United Kingdom, Wales
Monklands
General Hospital, Airdrie, Wales, ML6 0JF, United Kingdom;
Recruiting
J Murphy, MD
44-1236-748-748
Nevill
Hall Hospital, Gwent, Wales, United Kingdom; Recruiting
H W Habboush, MD
0873-732252 drhabboush@aol.com
Singleton
Hospital, Swansea, Wales, SA 2 8QA, United Kingdom; Recruiting
S. Al-Ismail, MD
44-1792-285-299 saad.al-ismail@swansea-tr.wales.nhs.uk
Ysbyty
Gwynedd, Bangor, Wales, LL57 2PW, United Kingdom; Recruiting
J R C Searle, MD
44-01-4838-4384
More Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Study ID Numbers CDR0000067454;
LRF-CLL4; LRG-MRC-LEUK-CLL4; EU-99030; MRC-LEUK-CLL4
Record last reviewed May 2003
NLM Identifier NCT00004218
ClinicalTrials.gov processed this record on
2004-06-01