Chlorambucil in Treating Patients With Advanced Chronic Lymphocytic Leukemia

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Unknown status

CT.gov ID

NCT00017108

Collaborator

(none)

Locations

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 chlorambucil regimen is more effective in treating advanced chronic lymphocytic leukemia.

PURPOSE: Randomized phase III trial to determine the effectiveness of different regimens of chlorambucil in treating patients who have advanced chronic lymphocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: chlorambucil Drug: cyclophosphamide Drug: fludarabine phosphate	Phase 3

Detailed Description

OBJECTIVES:

Compare overall and disease-related survival of patients with B-cell chronic lymphocytic leukemia treated with high-dose chlorambucil induction therapy with or without low-dose chlorambucil maintenance therapy.
Compare the time to salvage treatment in these patients treated with these regimens.
Compare the toxic effects of these regimens in these patients.
Compare the treatment-related mortality of these patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, time to complete response (before 12 weeks vs after 12 weeks vs partial response), and cytopenia at diagnosis (Binet stage A+B vs C).

All patients receive induction therapy comprising high-dose oral chlorambucil daily. Treatment continues until achievement of complete response or a maximum of 24 weeks in the absence of disease progression or unacceptable toxicity.

Patients who respond to induction therapy are randomized to 1 of 2 treatment arms for maintenance therapy.

Arm I: Patients receive low-dose oral chlorambucil twice a week. Therapy continues for up to 5 years in the absence of disease progression or unacceptable toxicity. If disease progression occurs, then patients may proceed to salvage therapy.
Arm II: Patients receive no maintenance therapy. If disease progresses, patients receive induction therapy again. If disease does not respond to re-induction therapy, then patients may proceed to salvage therapy.
Salvage therapy: Patients with progressive disease during maintenance therapy receive fludarabine IV daily and cyclophosphamide IV daily on days 1-3. Treatment repeats every 4 weeks for 3-6 courses.

Patients are followed monthly for 3 months, every 2 months for 6 months, and then every 3 months thereafter.

PROJECTED ACCRUAL: Approximately 470 patients will be accrued for this study within 4.7 years.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

Low Dose Chlorambucil Maintenance Vs. No Treatment Following High-Dose Chlorambucil Induction In Patients With Advanced B-Chronic Lymphocytic Leukemia. A Randomized Phase III Study Of The EORTC LG (CLL-3)

Study Start Date :

Mar 1, 2001

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of B-cell chronic lymphocytic leukemia
Co-expression of CD5/CD19 or CD5/CD20 positivity, dim sIg, and CD23 positivity
Previously untreated advanced disease defined as presence of at least 1 of the following:
Total tumor mass (TTM) score greater than 9
TTM doubling time less than 12 months
Bone marrow failure (platelet count less than 100,000/mm^3 and/or hemoglobin less than 10 g/dL)

PATIENT CHARACTERISTICS:

Age:

18 to 75

Performance status:

WHO 0-2

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics

Hepatic:

Bilirubin less than 3 times upper limit of normal (ULN)
Hepatitis B negative
No active hepatitis C

Renal:

Creatinine less than 3 times ULN OR
Creatinine clearance greater than 0.5 times normal

Cardiovascular:

No severe cardiovascular disease
No arrhythmia requiring chronic treatment
No New York Heart Association class III or IV congestive heart failure
No symptomatic ischemic heart disease

Other:

No uncontrolled systemic infection
HIV negative
No prior or concurrent uncontrolled malignancy
No prior or concurrent central nervous system or psychiatric disorders requiring hospitalization
No psychological, familial, sociological, or geographical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior biologic therapy

Chemotherapy:

No prior chemotherapy

Endocrine therapy:

Prior steroid therapy for less than 2 weeks allowed

Radiotherapy:

No prior radiotherapy

Surgery:

Not specified

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hopital Universitaire Erasme	Brussels	Belgium	1070
2	Cliniques Universitaires Saint-Luc	Brussels	Belgium	1200
3	Hopital de Jolimont	Haine Saint Paul	Belgium	7100
4	University Hospital - Olomouc	Olomouc	Czech Republic	775 20
5	County Hospital	Kaposvar	Hungary	H-7400
6	Azienda Ospedaliera Papardo	Messina	Italy
7	Ospedale Sant' Eugenio	Rome	Italy	00144
8	Clinical Center Skopje	Skopje	Macedonia, The Former Yugoslav Republic of	91000
9	Leyenburg Ziekenhuis	's-Gravenhage	Netherlands	2545 CH
10	Onze Lieve Vrouwe Gasthuis	Amsterdam	Netherlands	1091 HA
11	Leiden University Medical Center	Leiden	Netherlands	2300 CA
12	University Medical Center Nijmegen	Nijmegen	Netherlands	NL-6500 HB
13	Hospital Escolar San Joao	Porto	Portugal	4200