CLL-Irl Study. CTRIAL-IE (ICORG) 07-01, V7

July 4, 2025 updated by: Cancer Trials Ireland

An Open-label Phase II Study of the Efficacy and Safety of the Combination of Fludarabine, Cyclophosphamide and Rituximab in Patients With Chronic Lymphocytic Leukaemia Who Are Newly Diagnosed, Have Relapsed or Are Resistant to First-Line Treatment

RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, 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 fludarabine together with cyclophosphamide and rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying giving fludarabine together with cyclophosphamide and rituximab to see how well it works in treating patients with chronic lymphocytic leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Evaluate the efficacy, in terms of complete remission rate, of fludarabine phosphate, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia.

Secondary

  • Determine the time to treatment failure (TTF) in these patients.
  • Determine the overall survival of these patients until 10th January 2019.
  • Assess the predictive value of immunophenotype, hypermutation analysis, and FISH in determining TTF and OS in these patients.
  • Determine the safety profile of this regimen.

OUTLINE: This is a multicenter study.

Patients receive fludarabine IV over 30 minutes or orally and cyclophosphamide IV or orally on days 1-3 and pegfilgrastim subcutaneously on day 4. Starting on course 2, patients receive rituximab IV on day 1. Treatment repeats every 28 days for up to 6* courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients achieving negative minimal residual disease receive 4 courses of treatment.

Blood samples are collected periodically for biomarker analysis. Samples are analyzed for protein expression (i.e., CD38, CD20, and ZAP70) by flow cytometry; quantitative immunoglobulins, β2-microglobulin, and T-cell subsets by electrophoresis; IgVH mutation status; and cytogenetics (i.e., +12, del 13q, del 11q, and del 17p) by FISH.

After completion of study therapy, patients are followed every 6 months for 5 years and then annually until 10th January 2019.

Study Type

Interventional

Enrollment (Actual)

52

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

  • Ireland
      • Dublin, Ireland, 8
        • St. James's Hospital
      • Galway, Ireland
        • University College Hospital
      • Limerick, Ireland, 0009
        • University Hospital Limerick
      • Tullamore, Ireland
        • Midland Regional Hospital at Tullamore
      • Waterford, Ireland
        • Waterford Regional Hospital
    • Leinster
      • Dublin, Leinster, Ireland
        • Tallaght University Hospital
    • Munster
      • Cork, Munster, Ireland
        • Cork University Hospital

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

1 second to 64 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of chronic lymphocytic leukemia

    • Stage I-IV disease (Binet stage progressive A, B, C)
    • CD5 and CD23 positive
    • Untreated OR relapsed/resistant disease after combination chemotherapy or rituximab
    • No 17p deletion

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Life expectancy > 1 year
  • Creatinine clearance ≥ 50 mL/min
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other concurrent malignancy except for noninvasive cervical cancer or localized nonmelanomatous skin cancer
  • No history of anaphylaxis to mouse-derived humanized monoclonal antibody
  • No other severe concurrent (e.g., cardiac or pulmonary) diseases or mental disorders that could interfere with ability to participate in the study

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fludarabine, Cylophosphamide and Rituximab
Drug: cyclophosphamide
Genetic: gene expression analysis
Genetic: protein expression analysis
Other: laboratory biomarker analysis
Genetic: mutation analysis
Drug: fludarabine phosphate
Biological: rituximab
Other: flow cytometry
Genetic: cytogenetic analysis
Biological: pegfilgrastim
Genetic: fluorescence in situ hybridization

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Complete remission rate by NCI response criteria and minimal residual disease (MRD) analysis
Time Frame: A formal assessment of response by NCI Criteria (Appendix 3) with the addition of assessment of minimal residual disease in the marrow and if relevant assessment of bulky disease by CT scanning will be made after 4 +/-6 courses of therapy.
A formal assessment of response by NCI Criteria (Appendix 3) with the addition of assessment of minimal residual disease in the marrow and if relevant assessment of bulky disease by CT scanning will be made after 4 +/-6 courses of therapy.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to treatment failure (TFF)
Time Frame: A clinical assessment of response will be made after 4 courses of therapy, Patients with evidence of progressive disease will stop therapy and will be deemed to have failed treatment.
A clinical assessment of response will be made after 4 courses of therapy, Patients with evidence of progressive disease will stop therapy and will be deemed to have failed treatment.
Overall survival
Time Frame: Until 10th January 2019
Until 10th January 2019
Predictive value of immunophenotype, FISH, and hypermutation analysis in determining TTF and OS
Time Frame: See description

Timing and type of response assessment

During chemotherapy. A clinical assessment of response will be made after 4 courses of therapy. Patients with evidence of progressive disease will stop therapy and will be deemed to have failed treatment. A formal assessment of response by NCI Criteria (Appendix 3) with the addition of assessment of minimal residual disease in the marrow and if relevant assessment of bulky disease by CT scanning will be made after 4 +/-6 courses of therapy.

Following chemotherapy. Disease assessment after the end of therapy will involve a history(recording B-symptoms), complete physical examination, full blood count and blood MRD analysis every 6 months for 5 years and then annually until 10th of January 2019 or until disease progression.
See description
Acute and chronic toxicity as assessed by NCI criteria
Time Frame: A formal assessment of response by NCI Criteria (Appendix 3) with the addition of assessment of minimal residual disease in the marrow and if relevant assessment of bulky disease by CT scanning will be made after 4 +/-6 courses of therapy.
A formal assessment of response by NCI Criteria (Appendix 3) with the addition of assessment of minimal residual disease in the marrow and if relevant assessment of bulky disease by CT scanning will be made after 4 +/-6 courses of therapy.

Collaborators and Investigators

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

Sponsor

Cancer Trials Ireland

Investigators

  • Principal Investigator: Elisabeth Vandenberghe, MD, St. James's Hospital, Ireland

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

Helpful Links

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 (Actual)

August 18, 2008

Primary Completion (Actual)

November 21, 2019

Study Completion (Actual)

November 21, 2019

Study Registration Dates

First Submitted

December 19, 2008

First Submitted That Met QC Criteria

December 19, 2008

First Posted (Estimated)

December 22, 2008

Study Record Updates

Last Update Posted (Actual)

July 8, 2025

Last Update Submitted That Met QC Criteria

July 4, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTRIAL-IE (ICORG) 07-01
  • 2008-001250-40
  • EU-20898

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.

Clinical Trials on Leukemia

Clinical Trials on cyclophosphamide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Tunisia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe