Clinical trial NCT00337246: Combination Chemotherapy With or Without Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia
Official title: A Randomized Phase II Trial of Fludarabine, Cyclophosphamide and Mitoxantrone (FCM) With or Without Rituximab in Previously Treated Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: refractory chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-06-15
Enrollment: 56
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall response rate as measured by NCI Response Criteria
Secondary outcomes:
measure: Proportion of patients with undetectable minimal residual disease
measure: Progression-free survival at 2 years
measure: Overall survival at 2 years
measure: Toxicity
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: England
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: England
city: Carshalton
country: United Kingdom
facility: St Helier Hospital
state: England
city: Dartford Kent
country: United Kingdom
facility: Darent Valley Hospital
state: England
city: Gillingham Kent
country: United Kingdom
facility: Medway Maritime Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary at Leeds Teaching Hospital NHS Trust
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool and Broadgreen Hospitals NHS Trust
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
state: England
city: Truro, Cornwall
country: United Kingdom
facility: Royal Cornwall Hospital
state: England
city: Tunbridge Wells, Kent
country: United Kingdom
facility: Kent and Sussex Hospital
state: England
city: Wishaw
country: United Kingdom
facility: Wishaw General Hospital
state: England
city: Airdrie
country: United Kingdom
facility: Monklands General Hospital
state: Scotland
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
Study officials:
affiliation: Leeds General Infirmary
name: Peter Hillmen, MD
role: STUDY_CHAIR
References:
citation: Hillmen P, Cohen DR, Cocks K, Pettitt A, Sayala HA, Rawstron AC, Kennedy DB, Fegan C, Milligan DW, Radford J, Mercieca J, Dearden C, Ezekwisili R, Smith AF, Brown J, Booth GA, Varghese AM, Pocock C; NCRI CLL Sub-Group. A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia. Br J Haematol. 2011 Mar;152(5):570-8. doi: 10.1111/j.1365-2141.2010.08317.x. Epub 2011 Jan 14.