CLL-Irl Study. ICORG 07-01, V7

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier:
NCT00812669
First received: December 19, 2008
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Biological: pegfilgrastim
Biological: rituximab
Drug: cyclophosphamide
Drug: fludarabine phosphate
Genetic: cytogenetic analysis
Genetic: fluorescence in situ hybridization
Genetic: gene expression analysis
Genetic: mutation analysis
Genetic: protein expression analysis
Other: flow cytometry
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by ICORG- All Ireland Cooperative Oncology Research Group:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: at 10 years ] [ Designated as safety issue: No ]
  • Predictive value of immunophenotype, FISH, and hypermutation analysis in determining TTF and OS [ Time Frame: See description ] [ Designated as safety issue: No ]

    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 for 5 years or until disease progression.


  • 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. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 145
Study Start Date: August 2008
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine, Cylophosphamide and Rituximab Biological: pegfilgrastim Biological: rituximab Drug: cyclophosphamide Drug: fludarabine phosphate Genetic: cytogenetic analysis Genetic: fluorescence in situ hybridization Genetic: gene expression analysis Genetic: mutation analysis Genetic: protein expression analysis Other: flow cytometry Other: laboratory biomarker analysis

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 at 10 years.
  • 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 for 5 years.

  Eligibility

Ages Eligible for Study:   up to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00812669

Locations
Ireland
St. James's Hospital
Dublin, Ireland, 8
University College Hospital
Galway, Ireland
Mid-Western Cancer Centre at Mid-Western Regional Hospital
Limerick, Ireland, 0009
Midland Regional Hospital at Tullamore
Tullamore, Ireland
Waterford Regional Hospital
Waterford, Ireland
United Kingdom
St. George's Hospital
London, England, United Kingdom, SW17 ORE
Sponsors and Collaborators
ICORG- All Ireland Cooperative Oncology Research Group
Investigators
Principal Investigator: Elisabeth Vandenberghe, MD St. James's Hospital, Ireland
  More Information

Additional Information:
No publications provided

Responsible Party: ICORG- All Ireland Cooperative Oncology Research Group
ClinicalTrials.gov Identifier: NCT00812669     History of Changes
Other Study ID Numbers: CDR0000629790, ICORG-07-01, 2008-001250-40, EU-20898
Study First Received: December 19, 2008
Last Updated: January 23, 2014
Health Authority: Ireland: Irish Medicines Board

Keywords provided by ICORG- All Ireland Cooperative Oncology Research Group:
B-cell chronic lymphocytic leukemia
refractory chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine phosphate
Rituximab
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 19, 2014