Clinical trial NCT00049075: Fludarabine in Treating Patients With Chronic Lymphocytic Leukemia
Official title: A Phase II Study of Oral Fludarabine Phosphate in Patients With Previously Untreated B-Cell Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: B-cell 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: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 128
Sex: ALL
Minimum age (years): 16
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of fludarabine in treating patients who have chronic lymphocytic leukemia that has not been previously treated.

Detailed description: OBJECTIVES:

* Determine the overall response rate (complete and partial) in patients with previously untreated B-cell chronic lymphocytic leukemia treated with oral fludarabine.
* Determine the molecular complete response rate in patients who achieve a clinical or immunophenotypic complete response when treated with this drug.
* Determine the progression-free and treatment-free survival of patients treated with this drug.
* Determine the toxicity of this drug in these patients.
* Determine the baseline incidence of defined genetic abnormalities in patients treated with this drug.
* Determine the prognostic and predictive significance of defined genetic abnormalities in patients with respect to response to treatment with this drug.
* Determine the prognostic and predictive significance of immunophenotypic profile of patients with respect to response to treatment with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral fludarabine on days 1-5. Treatment repeats every 28 days for 6-8 courses in the absence of disease progression or unacceptable toxicity. Patients in complete remission after 6 courses do not receive further study therapy.

Patients are followed at 2 months and then every 4 months for 2 years.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Confirmed diagnosis of B-cell chronic lymphocytic leukemia (CLL)

  * Previously untreated
  * Rai stage I, II, III, or IV
  * Requiring systemic therapy
* Persistent lymphocytosis of greater than 5,000/mm\^3

  * Morphologically mature lymphocytes
* Monoclonal B-cell population

  * CD19/CD5/CD23 positive with kappa or lambda light chain restriction by immunophenotyping
* No other lymphoproliferative disorders including prolymphocytic leukemia, mantle cell lymphoma, progression to aggressive B-cell lymphoma, or Richter's syndrome
* No clinical autoimmune hematologic complication of CLL including Coomb's-positive hemolytic anemia or immune thrombocytopenia

  * Positive Coomb's test allowed if no clinical hemolysis

PATIENT CHARACTERISTICS:

Age

* 16 and over

Performance status

* ECOG 0-2

Life expectancy

* At least 6 months

Hematopoietic

* See Disease Characteristics

Hepatic

* Bilirubin no greater than 2 times upper limit of normal (ULN)
* AST and/or ALT no greater than 2 times ULN

Renal

* Creatinine no greater than 2 times ULN

Other

* Accessible for treatment and follow-up
* No known HIV infection
* No active bacterial, viral, or fungal infection requiring systemic antibiotics
* No conditions requiring corticosteroid therapy
* No history of other malignancies except for the following:

  * Adequately treated nonmelanoma skin cancer
  * Curatively treated carcinoma in situ of the cervix
  * Other solid tumors curatively treated with no evidence of disease within the past 5 years
* No other major medical illness that would preclude study
* No known hypersensitivity to fludarabine or its components
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for at least 6 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent immunotherapy including monoclonal antibody therapy
* No concurrent autologous or allogeneic stem cell or bone marrow transplantation

Chemotherapy

* No other concurrent cytotoxic drugs

Endocrine therapy

* No concurrent corticosteroids except inhaled or topical corticosteroids

  * No concurrent corticosteroids for nausea prophylaxis

Radiotherapy

* No prior radiotherapy affecting more than 25% of bone marrow and/or involving the pelvic area
* No concurrent radiotherapy

Surgery

* Not specified

Other

* At least 4 weeks since prior investigational agents
* No other concurrent investigational agents

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Center - Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: Providence Health Care - Vancouver
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Moncton
country: Canada
facility: Moncton Hospital
state: New Brunswick
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: St. Johns
country: Canada
facility: Newfoundland Cancer Treatment and Research Foundation
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Margaret and Charles Juravinski Cancer Centre
state: Ontario
city: Kingston
country: Canada
facility: Kingston Regional Cancer Centre
state: Ontario
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Centre
state: Ontario
city: London
country: Canada
facility: Cancer Care Ontario-London Regional Cancer Centre
state: Ontario
city: Mississauga
country: Canada
facility: Credit Valley Hospital
state: Ontario
city: Oshawa
country: Canada
facility: Durham Regional Cancer Centre at Lakeridge Health Oshawa
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Sault Sainte Marie
country: Canada
facility: Algoma Reginal Cancer Program at Sault Area Hospital
state: Ontario
city: St. Catharines
country: Canada
facility: Hotel Dieu Health Sciences Hospital - Niagara
state: Ontario
city: Sudbury
country: Canada
facility: Northeastern Ontario Regional Cancer Centre, Sudbury
state: Ontario
city: Thunder Bay
country: Canada
facility: Northwestern Ontario Regional Cancer Centre, Thunder Bay
state: Ontario
city: Toronto
country: Canada
facility: Toronto Sunnybrook Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Joseph's Health Centre - Toronto
state: Ontario
city: Weston
country: Canada
facility: Humber River Regional Hospital - Weston
state: Ontario
city: Windsor
country: Canada
facility: Cancer Care Ontario - Windsor Regional Cancer Centre
state: Ontario
city: Fleurimont
country: Canada
facility: CHUS-Hopital Fleurimont
state: Quebec
city: Greenfield Park
country: Canada
facility: Hopital Charles Lemoyne
state: Quebec
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Quebec City
country: Canada
facility: Hopital de L'Enfant Jesus
state: Quebec
city: Quebec City
country: Canada
facility: Hopital du Saint-Sacrement, Quebec
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Le Mans
country: France
facility: Centre Jean Bernard
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
Study officials:
affiliation: Margaret and Charles Juravinski Cancer Centre
name: Ralph M. Meyer, MD, FRCPC
role: STUDY_CHAIR
References:
citation: Shustik C, Turner AR, Desjardins P, Fernandez L, Rubin S, Larratt L, Duncan AM, Rizi D, Sadura A, Shepherd L, Li D, Rassenti L, Kipps T. Oral fludarabine in untreated patients with B-cell chronic lymphocytic leukemia. Leukemia. 2010 Jan;24(1):237-9. doi: 10.1038/leu.2009.205. Epub 2009 Oct 8. No abstract available.