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

Cancer Trials Ireland

Status and phase: Completed; Phase 2

Conditions: Leukemia

Treatments: Genetic: fluorescence in situ hybridization; Genetic: protein expression analysis; Genetic: cytogenetic analysis; Other: laboratory biomarker analysis; Other: flow cytometry; Biological: pegfilgrastim; Genetic: mutation analysis; Genetic: gene expression analysis; Biological: rituximab; Drug: cyclophosphamide; Drug: fludarabine phosphate

Study type: Interventional

Funder types: NETWORK

Identifiers

NCT00812669

CTRIAL-IE (ICORG) 07-01

2008-001250-40

EU-20898

Details and patient eligibility

About

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.

Full 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.

Enrollment: 52 patients

Sex: All

Ages: Under 64 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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52 participants in 1 patient group

Fludarabine, Cylophosphamide and Rituximab

Experimental group

Treatment:

Drug: fludarabine phosphate

Drug: cyclophosphamide

Biological: rituximab

Genetic: mutation analysis

Genetic: gene expression analysis

Other: flow cytometry

Biological: pegfilgrastim

Other: laboratory biomarker analysis

Genetic: protein expression analysis

Genetic: cytogenetic analysis

Genetic: fluorescence in situ hybridization