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

August 1, 2013 updated by: Cancer Research UK

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

56

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall response rate as measured by NCI Response Criteria

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cancer Research UK

Investigators

  • Study Chair: Peter Hillmen, MD, Leeds General Infirmary

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2005

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

June 13, 2006

First Submitted That Met QC Criteria

June 13, 2006

First Posted (Estimate)

June 15, 2006

Study Record Updates

Last Update Posted (Estimate)

August 2, 2013

Last Update Submitted That Met QC Criteria

August 1, 2013

Last Verified

May 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTRU-NCRI-UKCLL01-FCM/FCM-R
  • CDR0000485181 (Registry Identifier: PDQ (Physician Data Query))
  • EU-20626
  • ROCHE-NCRI-UKCLL01-FCM/FCM-R
  • ISRCTN77546448
  • EUDRACT-2004-003982-34

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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