Fludarabine, Cyclophosphamide, and Rituximab or Alemtuzumab in Treating CLL2007 CLL 2007 FMP

Leukemia Clinical Trial

Official title:

Randomized Phase-III Trial Comparing Fludarabine and Cyclophosphamide Plus Rituximab (FCR) to FC and MabCampath (FCCam) for Previously Untreated Fit Patients With Chronic Lymphocytic Leukemia (CLL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00564512
• Other study ID #: CDR0000577580
• Secondary ID: CLL-2007-FMP
• Status: Completed
• Phase: Phase 3
• First received: November 27, 2007
• Last updated: July 24, 2013
• Start date: November 2007
• Est. completion date: July 2013

Study information

• Verified date: April 2009
• Source: French Innovative Leukemia Organisation
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to kill cancer cells or stop them from growing. Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. It is not yet known whether giving fludarabine and cyclophosphamide together with rituximab is more effective than giving fludarabine and cyclophosphamide together with alemtuzumab in treating B-cell chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying giving fludarabine together with cyclophosphamide and rituximab to see how well it works as first-line therapy compared with giving fludarabine together with cyclophosphamide and alemtuzumab in treating patients with B-cell chronic lymphocytic leukemia.

Description:

OBJECTIVES:

Primary

• To compare 36-month progression-free survival in patients with Binet stage B or C B-cell chronic lymphocytic leukemia treated with first-line therapy comprising fludarabine phosphate and cyclophosphamide and either rituximab or alemtuzumab.

Secondary

• To compare the disease-free survival, event-free survival, and overall survival of patients treated with these regimens.

• To compare time to next treatment in patients treated with these regimens.

• To compare the overall response rate (complete response [CR] and partial response [PR]) in patients treated with these regimens.

• To compare the rate of phenotypic and molecular response in patients treated with these regimens.

• To compare the duration of phenotypic, molecular, complete and partial responses in patients treated with these regimens.

• To compare the response rates and survival times in biological subgroups.

• To compare the rates of treatment-related adverse effects in patients treated with these regimens.

• To compare the quality of life of patients treated with these regimens.

• Minimal residual disease study.

OUTLINE: This is a multicenter study. Patients are stratified according to Ig mutational status and cytogenetic abnormalities. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive rituximab IV on day 1 and fludarabine phosphate and cyclophosphamide IV or orally on days 2-4 of course 1. Beginning in course 2 and for all subsequent courses, patients receive rituximab IV on day 1 and fludarabine phosphate and cyclophosphamide IV or orally on days 1-3.

• Arm II: Patients receive alemtuzumab subcutaneously, oral fludarabine phosphate, and oral cyclophosphamide on days 1-3.

In both arms, treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 178
• Est. completion date: July 2013
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

DISEASE CHARACTERISTICS:

Inclusion

Diagnosis of B-cell chronic lymphocytic leukemia (CLL), meeting the following criteria:

• Binet classification stages B or C

• Del 17 p (FISH) negative (< 10 % positives cores)

• Matutes score 4 or 5

Exclusion Transformation to aggressive B-cell malignancy (e.g. diffuse large cell lymphoma, Hodgkin lymphoma, or prolymphocytic leukemia)

PATIENT CHARACTERISTICS:

Exclusion ECOG performance status = 2

• Life expectancy < 6 months

• Creatinine clearance < 60 mL/min

• Total bilirubin > 2 x upper limit of normal (ULN)

• Gamma glutamyltransferase or transaminase levels > 2 x ULN

• Cumulative illness rating scale > 6

• HIV seropositivity

• Hepatitis B or C seropositivity (unless clearly due to vaccination)

• Clinically significant autoimmune anemia

• Active bacterial, viral, or fungal infection

• Active second malignancy currently requiring treatment (except basal cell carcinoma or in situ endometrial carcinoma) and/or less than 5 years complete remission after breast cancer

• Any severe comorbid conditions including, but not limited to, any of the following:

• Class III or IV heart failure

• Recent myocardial infarction

• Unstable angina

• Ventricular tachyarrhythmias requiring ongoing treatment

• Severe chronic obstructive pulmonary disease with hypoxemia

• Uncontrolled diabetes mellitus

• Uncontrolled hypertension

• Concomitant disease requiring prolonged use of corticosteroids (> 1 month)

• Known hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the study drugs

• Contraindication to the use of rituximab or alemtuzumab according to Summary of Product Characteristics

• Any coexisting medical or psychological condition that would preclude participation in the required study procedures

• Any mental deficiency preventing proper understanding of the requirements of treatment

• Person under law control

• Pregnant or breastfeeding women

• Fertile patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study

PRIOR CONCURRENT THERAPY:

Inclusion

• No prior chemotherapy, radiotherapy, or immunotherapy for CLL

• Corticosteroids within the past month allowed

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Biological:
• Campath
Fludarabine-Cyclophosphamide-Campath (FCCam)
• rituximab
Fludarabine-Cyclophosphamide-Rituximab (FCR)

Drug:
• cyclophosphamide
Fludarabine-Cyclophosphamide-Campath (FCCAM) Fludarabine-Cyclophosphamide-Rituximab (FCR)
• fludarabine
Fludarabine-Cyclophosphamide-Campath (FCCAM) Fludarabine-Cyclophosphamide-Rituximab (FCR)

Locations

Country	Name	City	State
France	Centre Henri Becquerel	Rouen

Sponsors (1)

Lead Sponsor	Collaborator
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival at 36 months		36 months follow up	No
Secondary	Disease-free survival		36 months follow up	No
Secondary	Event-free survival		36 months follow up	No
Secondary	Overall survival		36 months follow up	No
Secondary	Time to next treatment		36 months follow up	No
Secondary	Overall response rate (complete response [CR] and partial response [PR])		36 months follow up	No
Secondary	Duration of phenotypic, molecular, NCI complete and partial responses		36 months follow up	No
Secondary	Response rates and survival times in biological subgroups		36 months follow up	No
Secondary	Treatment-related adverse effects		36 months follow up	Yes