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

Cancer Trials Ireland52 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Eligibility

Sex: ALLMin age: 0 YearsMax age: 64 Years

Medical Language ↔ Plain English

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

Locations (7)

Tallaght University Hospital

Dublin, Leinster, Ireland

Cork University Hospital

Cork, Munster, Ireland

St. James's Hospital

Dublin, Ireland

University College Hospital

Galway, Ireland

University Hospital Limerick

Limerick, Ireland

Midland Regional Hospital at Tullamore

Tullamore, Ireland

Waterford Regional Hospital

Waterford, Ireland

Outcomes

Primary Outcomes

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.

Secondary Outcomes

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.

Overall survival

Time frame: Until 10th January 2019

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.

Time frame: See description

Acute and chronic toxicity as assessed by NCI criteria