Chemotherapy in Treating Patients With Newly Diagnosed Chronic Lymphocytic Leukemia

Sponsor

Leukemia Research Fund (Other)

Overall Status

Completed

CT.gov ID

NCT00004218

Collaborator

Medical Research Council (Other)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known which regimen of chemotherapy is more effective for chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying chlorambucil to see how well it works compared to fludarabine and cyclophosphamide or fludarabine alone in treating patients with newly diagnosed chronic lymphocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: chlorambucil Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: fludarabine phosphate Drug: prednisolone Drug: vincristine sulfate	Phase 3

Detailed Description

OBJECTIVES:

Compare the survival rate of patients with newly diagnosed chronic lymphocytic leukemia treated with chlorambucil alone vs fludarabine with or without cyclophosphamide.
Compare the response rate and duration of remission in patients treated with these regimens.
Compare the toxic effects of these regimens in these patients.
Compare the quality of life of patients treated with these regimens.
Determine the impact of the drug response information provided by the DiSC assay on response rate and survival in relapsed or nonresponding patients.
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.

First randomization:
Arm I: Patients receive oral chlorambucil daily for 7 days. Treatment repeats every 4 weeks until maximum response or up to 1 year.
Arm II: Patients receive fludarabine IV or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses.
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.

Second randomization:
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.
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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

Chronic Lymphocytic Leukemia Trial 4: A Randomized Comparison of Chlorambucil, Fludarabine and Fludarabine Plus Cyclophosphamide

Study Start Date :

Oct 1, 1999

Actual Study Completion Date :

Jul 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of B-cell chronic lymphocytic leukemia (CLL) requiring therapy and meeting the following criteria:
Previously untreated disease
Peripheral blood morphology, excluding other leukemia and low-grade lymphoma in leukemic phase
Cell markers: CD5+, CD23+, SmIg (weak), CD79b-, FMC7-
Persistent lymphocytosis (greater than 10,000/mm^3)
At least 40% bone marrow infiltration
Stage 0 or I progressive disease indicated by at least one of the following:
Persistent rise in lymphocyte count with doubling time less than 12 months
Downward trend in hemoglobin and/or platelet count
At least 50% increase in size of liver and/or spleen and/or lymph nodes
Appearance of lymphadenopathy, hepatomegaly, or splenomegaly
Constitutional symptoms caused by disease
Pyrexia
Night sweats
Weight loss OR
Stage II or III

PATIENT CHARACTERISTICS:

Age:

Not specified

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics

Hepatic:

Bilirubin no greater than 2 times upper limit of normal (ULN)*
SGOT/SGPT no greater than 2 times ULN* NOTE: * Unless due to CLL

Renal:

Creatinine clearance at least 30 mL/min

Other:

No other cancer or life-threatening disease
Not pregnant
Fertile patients must use effective contraception during and for 6 months after study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

No concurrent corticosteroids (e.g., dexamethasone) as antiemetics

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Italiano de Buenos Aires	Buenos Aires		Argentina	CP1181ACH
2	Hospital Alvarez	Buenos Aires		Argentina
3	University Hospital Rebro	Zagreb		Croatia	10000
4	University of Ioannina	Ioannina		Greece	GR-45110
5	University of Patras Medical School	Rio Patras		Greece	GR-26500
6	St. James' Hospital	Dublin		Ireland	8
7	Galway University Hospital	Galway		Ireland
8	Ospedali Riuniti di Bergamo	Bergamo		Italy	24100
9	Canterbury Health Laboratories	Christchurch		New Zealand
10	Russian Academy of Medical Sciences Cancer Research Center	Moscow		Russian Federation	115478
11	Stoke Mandeville Hospital	Aylesbury-Buckinghamshire	England	United Kingdom	HP21 8AL
12	Horton Hospital	Banbury	England	United Kingdom	OX16 9A
13	North Hampshire Hospital	Basingstoke	England	United Kingdom	RG24 9NA
14	Selly Oak Hospital at University Hospital NHS Trust	Birmingham	England	United Kingdom	B29 6JD
15	Birmingham Heartlands Hospital	Birmingham	England	United Kingdom	B9 5SS
16	Blackpool Victoria Hospital	Blackpool	England	United Kingdom	FY3 8NR
17	Royal Bournemouth Hospital	Bournemouth	England	United Kingdom	BH7 7DW
18	Bradford Hospitals NHS Trust	Bradford	England	United Kingdom	BD9 6RJ
19	Royal Sussex County Hospital	Brighton	England	United Kingdom	BN2 5BE
20	Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust	Cambridge	England	United Kingdom	CB2 2QQ
21	St Helier Hospital	Carshalton	England	United Kingdom	SM5 1AA
22	Chesterfield Royal Hospital	Chesterfield	England	United Kingdom	S44 5BL
23	Countess of Chester Hospital	Chester	England	United Kingdom	CH2 1UL
24	Saint Richards Hospital	Chichester	England	United Kingdom	P019 4SE
25	Darlington Memorial	Darlington	England	United Kingdom	DL3 6HX
26	Dartford & Gravesham NHS Trust, Joyce Green Hospital	Dartford Kent	England	United Kingdom	DA1 5PL
27	Doncaster Royal Infirmary	Doncaster	England	United Kingdom	DN2 5LT
28	Russells Hall Hospital	Dudley	England	United Kingdom	DY1 2HQ
29	Bishop Auckland Hospital	Durham	England	United Kingdom
30	Epsom General Hospital	Epsom Surrey	England	United Kingdom	KT18 7E9
31	Queen Elizabeth Hospital	Gateshead-Tyne and Wear	England	United Kingdom	NE9 6SX
32	Queen Elizabeth Hospital	Gateshead	England	United Kingdom	NE9 6SX
33	Gloucester Royal NHS Trust - Glouchester Royal Hospital	Gloucester	England	United Kingdom	GL1 3NN
34	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England	United Kingdom	GU2 5XX
35	Harrogate District Hospital	Harrogate	England	United Kingdom	HG2 7SX
36	Hemel Hempstead General	Hemel Hempstead	England	United Kingdom
37	Institute of Oncology and Radiology of Serbia	High Wycombe	England	United Kingdom
38	Huddersfield Royal Infirmary	Huddersfield, West Yorks	England	United Kingdom	HD3 3EA
39	Hull Royal Infirmary	Hull	England	United Kingdom	HU3 2KZ
40	Clinical Trials and Research Unit of the University of Leeds	Leeds	England	United Kingdom	LS2 9N9
41	Leicester Royal Infirmary	Leicester	England	United Kingdom	LE1 5WW
42	Royal Liverpool and Broadgreen Hospitals	Liverpool	England	United Kingdom	L7 8XP
43	Walton General Hospital	Liverpool	England	United Kingdom	L9 1AE
44	Aintree University Hospital	Liverpool	England	United Kingdom	L9 7AL
45	Whipps Cross Hospital	London	England	United Kingdom	E11 1NR
46	Royal Free and University College Medical School	London	England	United Kingdom	NW1 2QG
47	Guy's and St. Thomas' Hospitals NHS Foundation Trust	London	England	United Kingdom	SE1 9RT
48	St. George's Hospital	London	England	United Kingdom	SW17 0QT
49	Royal Marsden NHS Foundation Trust - London	London	England	United Kingdom	SW3 6JJ
50	West Middlesex Hospital	Middlesex	England	United Kingdom	N18 1QZ
51	Northern Cancer Network	Newcastle-Upon-Tyne	England	United Kingdom	NE27 OQJ
52	Northampton General Hospital NHS Trust	Northampton	England	United Kingdom	NN1 5BD
53	Bassetlaw Hospital & Community Services NHS Trust	Nottinghamshire	England	United Kingdom	S81 3SA
54	Nottingham City Hospital NHS Trust	Nottingham	England	United Kingdom	NG5 1PB
55	Farnborough Hospital	Orpington Kent	England	United Kingdom	BR6 8ND
56	Wharfdale General Hospital	Otley	England	United Kingdom	LS21 7AA
57	Pontefract General Infirmary	Pontefract West Yorkshire	England	United Kingdom	WF8 1PL
58	Berkshire Cancer Centre at Royal Berkshire Hospital	Reading	England	United Kingdom	RG1 5AN
59	Oldchurch Hospital	Romford	England	United Kingdom	RM7 OBE
60	Rotherham District General Hospital - NHS Trust	Rotherham	England	United Kingdom	S60 2UD
61	Conquest Hospital	Saint Leonards-on-Sea	England	United Kingdom	TN37 7RD
62	Scunthorpe General Hospital	Scunthorpe	England	United Kingdom	DN15 7BH
63	Royal South Hants Hospital	Southampton	England	United Kingdom	SO14 0YG
64	Southampton General Hospital	Southampton	England	United Kingdom	SO16 6YD
65	Staffordshire General Hospital	Stafford	England	United Kingdom	ST16 3SA
66	North Staffs Royal Infirmary	Stoke-On-Trent	England	United Kingdom	ST4 7LN
67	St. Peter's Hospital NHS Trust	Surrey	England	United Kingdom	KT 16 OPZ
68	Torbay Hospital	Torquay Devon	England	United Kingdom	TQ2 7AA
69	City Hospital - Birmingham	West Bromwich	England	United Kingdom	B71 4HJ
70	Good Hope Hospital Trust	West Midlands	England	United Kingdom	B75 7RR
71	Worthing Hospital	Worthing	England	United Kingdom	BN11 2DH
72	Cancer Care Centre at York Hospital	York	England	United Kingdom	Y031 8HE
73	Belfast City Hospital Trust	Belfast	Northern Ireland	United Kingdom	BT9 7AB
74	Ulster Hospital	Dundonald	Northern Ireland	United Kingdom	BT16
75	Craigavon Area Hospital	Portadown, Craigavon	Northern Ireland	United Kingdom	BT63 5QQ
76	Aberdeen Royal Infirmary	Aberdeen	Scotland	United Kingdom	AB25 2ZN
77	Monklands General Hospital	Airdrie	Scotland	United Kingdom	ML6 0JF
78	Dumfries Royal Infirmary	Dumfries	Scotland	United Kingdom	DG1 4AP
79	Western General Hospital	Edinburgh	Scotland	United Kingdom	EH4 2XU
80	Southern General Hospital	Glasgow	Scotland	United Kingdom	G51 4TF
81	Raigmore Hospital	Inverness	Scotland	United Kingdom	1V2 3UJ
82	Victoria Hospital	Kirkcaldy	Scotland	United Kingdom	KY2 5AH
83	Royal Alexandra Hospital	Paisley	Scotland	United Kingdom
84	Ysbyty Gwynedd	Bangor	Wales	United Kingdom	LL57 2PW
85	Nevill Hall Hospital	Gwent	Wales	United Kingdom
86	Singleton Hospital	Swansea	Wales	United Kingdom	SA 2 8QA