Clinical trial NCT00812669: CLL-Irl Study. CTRIAL-IE (ICORG) 07-01, V7
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
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
Lead sponsor: Cancer Trials Ireland
Sponsor class: NETWORK
First posted: 2008-12-22
Enrollment: 52
Sex: ALL
Minimum age (years): 0
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Complete remission rate by NCI response criteria and minimal residual disease (MRD) analysis
timeFrame: 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:
measure: Time to treatment failure (TFF)
timeFrame: 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.
measure: Overall survival
timeFrame: Until 10th January 2019
measure: Predictive value of immunophenotype, FISH, and hypermutation analysis in determining TTF and OS
timeFrame: See description
measure: Acute and chronic toxicity as assessed by NCI criteria
timeFrame: 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.
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Tallaght University Hospital
state: Leinster
city: Cork
country: Ireland
facility: Cork University Hospital
state: Munster
city: Dublin
country: Ireland
facility: St. James's Hospital
city: Galway
country: Ireland
facility: University College Hospital
city: Limerick
country: Ireland
facility: University Hospital Limerick
city: Tullamore
country: Ireland
facility: Midland Regional Hospital at Tullamore
city: Waterford
country: Ireland
facility: Waterford Regional Hospital
Study officials:
affiliation: St. James's Hospital, Ireland
name: Elisabeth Vandenberghe, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Appleby N, O'Brien D, Quinn FM, Smyth L, Kelly J, Parker I, Scott K, Cahill MR, Crotty G, Enright H, Hennessy B, Hodgson A, Leahy M, O'Leary H, O'Dwyer M, Hayat A, Vandenberghe EA. Risk adjusted therapy in chronic lymphocytic leukemia: a phase II cancer trials Ireland (CTRIAL-IE [ICORG 07-01]) study of fludarabine, cyclophosphamide, and rituximab therapy evaluating response adapted, abbreviated frontline therapy with FCR in non-del(17p) CLL. Leuk Lymphoma. 2018 Jun;59(6):1338-1347. doi: 10.1080/10428194.2017.1376746. Epub 2017 Sep 19.