Combination Chemotherapy With or Without Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

Sponsor

Cancer Research UK (Other)

Overall Status

Completed

CT.gov ID

NCT00337246

Collaborator

(none)

Enrollment

Locations

Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving combination chemotherapy together with rituximab may kill more cancer cells. It is not yet known whether giving combination chemotherapy together with rituximab is more effective than combination chemotherapy alone in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase II trial is studying how well giving combination chemotherapy with or without rituximab works in treating patients with previously treated chronic lymphocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: rituximab Drug: cyclophosphamide Drug: fludarabine phosphate Drug: mitoxantrone hydrochloride	Phase 2

Detailed Description

OBJECTIVES:

Primary

Assess the efficacy and safety of fludarabine, cyclophosphamide, and mitoxantrone hydrochloride with or without rituximab in patients with previously treated chronic lymphocytic leukemia.
Determine the overall response rate, defined as complete or partial remission, in these patients.

Secondary

Determine the proportion of patients with undetectable minimal residual disease.
Determine the 2-year progression-free survival of these patients.
Determine the 2-year overall survival of these patients.
Determine the toxicity of this regimen.

OUTLINE: This is a randomized, controlled, open-label, parallel group, multicenter study. Patients are stratified according to prior treatment with fludarabine (refractory vs not refractory or naive). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral fludarabine* and oral cyclophosphamide* on days 1-5 and mitoxantrone hydrochloride IV on day 1.
Arm II: Patients receive fludarabine*, cyclophosphamide*, and mitoxantrone hydrochloride as in arm I. Patients also receive rituximab IV on day 1.

NOTE: *If the oral regimen is not tolerated, patients may receive fludarabine IV and cyclophosphamide IV on days 1-3.

Treatment in both arms repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 3 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

56 participants

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Trial of Fludarabine, Cyclophosphamide and Mitoxantrone (FCM) With or Without Rituximab in Previously Treated Chronic Lymphocytic Leukemia

Study Start Date :

Jul 1, 2005

Actual Study Completion Date :

Mar 1, 2011

Outcome Measures

Primary Outcome Measures

Overall response rate as measured by NCI Response Criteria []

Secondary Outcome Measures

Proportion of patients with undetectable minimal residual disease []
Progression-free survival at 2 years []
Overall survival at 2 years []
Toxicity []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of chronic lymphocytic leukemia requiring therapy
Previously treated with ≥ 1 chemotherapeutic regimen

PATIENT CHARACTERISTICS:

WHO performance status 0-2
Life expectancy ≥ 12 weeks
Creatinine clearance ≥ 30 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile female patients must use effective contraception for 4 weeks before, during, and for 6 months after completion of study treatment
Fertile male patients must use effective contraception during and for 6 months after completion of study treatment
No history of anaphylaxis after exposure to rat or mouse-derived complementary-determining region (CDR)-grafted humanized monoclonal antibodies
No toxicity attributable to purine analogues (e.g., autoimmune hemolytic anemia, neurological toxicity, or allergy)
No active infection
No other severe (particularly cardiac or pulmonary) diseases or mental disorders that would preclude study participation

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior fludarabine (or other purine analogues) combined with cyclophosphamide and mitoxantrone hydrochloride
No prior rituximab, either alone or in combination with chemotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Heartlands Hospital	Birmingham	England	United Kingdom	B9 5SS
2	Blackpool Victoria Hospital	Blackpool	England	United Kingdom	FY3 8NR
3	Kent and Canterbury Hospital	Canterbury	England	United Kingdom	CT2 7NR
4	St Helier Hospital	Carshalton	England	United Kingdom	SM5 1AA
5	Darent Valley Hospital	Dartford Kent	England	United Kingdom	DA2 8DA
6	Medway Maritime Hospital	Gillingham Kent	England	United Kingdom	ME7 5NY
7	Leeds General Infirmary at Leeds Teaching Hospital NHS Trust	Leeds	England	United Kingdom	LS1 3EX
8	Leicester Royal Infirmary	Leicester	England	United Kingdom	LE1 5WW
9	Royal Liverpool and Broadgreen Hospitals NHS Trust	Liverpool	England	United Kingdom	L7 8XP
10	Maidstone Hospital	Maidstone	England	United Kingdom	ME16 9QQ
11	Christie Hospital NHS Trust	Manchester	England	United Kingdom	M20 4BX
12	Royal Cornwall Hospital	Truro, Cornwall	England	United Kingdom	TR1 3LJ
13	Kent and Sussex Hospital	Tunbridge Wells, Kent	England	United Kingdom	TN4 8AT
14	Wishaw General Hospital	Wishaw	England	United Kingdom	ML2 0DP
15	Monklands General Hospital	Airdrie	Scotland	United Kingdom	ML6 0JF
16	University Hospital of Wales	Cardiff	Wales	United Kingdom	CF14 4XW