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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00812669
• Other study ID #: CTRIAL-IE (ICORG) 07-01
• Secondary ID: CTRIAL-IE (ICORG
• Status: Completed
• Phase: Phase 2
• Start date: August 18, 2008
• Est. completion date: November 21, 2019

Study information

• Verified date: April 2023
• Source: Cancer Trials Ireland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: November 21, 2019
• Est. primary completion date: November 21, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 64 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell

Intervention

Biological:
• pegfilgrastim

• rituximab

Drug:
• cyclophosphamide

• fludarabine phosphate

Genetic:
• cytogenetic analysis

• fluorescence in situ hybridization

• gene expression analysis

• mutation analysis

• protein expression analysis

Other:
• flow cytometry

• laboratory biomarker analysis

Locations

Country	Name	City	State
Ireland	Cork University Hospital	Cork	Munster
Ireland	St. James's Hospital	Dublin
Ireland	Tallaght University Hospital	Dublin	Leinster
Ireland	University College Hospital	Galway
Ireland	University Hospital Limerick	Limerick
Ireland	Midland Regional Hospital at Tullamore	Tullamore
Ireland	Waterford Regional Hospital	Waterford

Sponsors (1)

Lead Sponsor	Collaborator
Cancer Trials Ireland

Country where clinical trial is conducted

Ireland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete remission rate by NCI response criteria and minimal residual disease (MRD) analysis		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	Time to treatment failure (TFF)		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.
Secondary	Overall survival		Until 10th January 2019
Secondary	Predictive value of immunophenotype, FISH, and hypermutation analysis in determining TTF and OS	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
Secondary	Acute and chronic toxicity as assessed by NCI criteria		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.

External Links

•   Summary of Clinical trial findings published in "Leukemia and Lymphoma".