Leukemia
Conditions
Keywords
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
Brief 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.
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.
Interventions
BIOLOGICALpegfilgrastim
BIOLOGICALrituximab
DRUGcyclophosphamide
DRUGfludarabine phosphate
GENETICcytogenetic analysis
GENETICfluorescence in situ hybridization
GENETICgene expression analysis
GENETICmutation analysis
GENETICprotein expression analysis
OTHERflow cytometry
OTHERlaboratory biomarker analysis
Sponsors
Cancer Trials Ireland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 64 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | — |
| Overall survival | Until 10th January 2019 | — |
| Predictive value of immunophenotype, FISH, and hypermutation analysis in determining TTF and OS | 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. |
| 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. | — |
Countries
Ireland
Outcome results
None listed