Prospective, randomized trial of cell culture drug resistance testing (CCDRT, "chemosensitivity testing") in chronic lymphocytic leukemia (CLL)

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:

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:

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

           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

           University Hospital Rebro, Zagreb,  10000,  Croatia; Recruiting
         I. Radman, MD  385-1-238-8277

           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

           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

           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

     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

           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

           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

           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

           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

           Epsom General Hospital, Epsom Surrey,  England,  KT18 7E9,  United Kingdom; Recruiting
         Lydia Jones, MD, BSc, BS, FRCP, FRCPath  44-1372-735-735

           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

           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

           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

           Leicester Royal Infirmary, Leicester,  England,  LE1 5WW,  United Kingdom; Recruiting
         M.J. Dyer, MD  44-116-252-3222

           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

           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

           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

           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

           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

           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

           Southampton General Hospital, Southampton,  England,  SO16 6YD,  United Kingdom; Recruiting
         K Orchard, MD  440-238-079-4118

           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

           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

           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

           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

           Dumfries Royal Infirmary, Dumfries,  Scotland,  DG1 4AP,  United Kingdom; Recruiting
         R K B Dang, MD  44-1387-241-441

           Raigmore Hospital, Inverness,  Scotland,  1V2 3UJ,  United Kingdom; Recruiting
         C J Lush, MD  463-704258

           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

     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

           Singleton Hospital, Swansea,  Wales,  SA 2 8QA,  United Kingdom; Recruiting
         S. Al-Ismail, MD  44-1792-285-299

           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 processed this record on 2004-06-01