Clinical trial NCT01263704: A Study of MabThera/Rituxan (Rituximab) in Combination With Fludarabine And Cyclophosphamide as Primary Therapy in Elderly Patients With Chronic Lymphocytic Leukemia
Official title: A Phase II, Multicenter, Single Arm Study to Determine the Efficacy and Safety of Low Dose Fludarabine and Cyclophosphamide Combined With Standard Dose Rituximab as Primary Therapy in Elderly Untreated Patients (>/=65 Years Old) With Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphocytic Leukemia, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-12-21
Enrollment: 42
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This single arm, open-label study will assess the safety and efficacy of low dose fludarabine and cyclophosphamide in combination with standard dose MabThera/Rituxan (rituximab) as primary therapy in elderly patients (\>/= 65 years) with chronic lymphocytic leukemia. Patients will receive six 28-day cycles of treatment with Mabthera/Rituxan (375 mg/m2 intravenously \[iv\] Day 0 of cycle 1, 500 mg/m2 iv Day 1 of cycles 2-6), fludarabine (12.5 mg/m2/d iv Days 1-3, cycles 1-6) and cyclophosphamide (150 mg/m2/d iv Days 1-3, cycles 1-6). Anticipated time on study treatment is 6 months, with a 30-month follow-up period.


Eligibility criteria: Inclusion Criteria:

* Adult patients, \>/= 65 years of age
* Previously untreated B-cell chronic lymphocytic leukemia (CLL)
* Binet stage C or active Binet stage A and B disease

Exclusion Criteria:

* Prior treatment for CLL
* CLL with transformation (Richter's syndrome)
* Suspected or known central nervous system (CNS) involvement of CLL
* Impaired renal or hepatic function
* Human Immunodeficiency Virus (HIV) positivity, active hepatitis B/C or Hepatitis B Virus (HBV) surface antigen positive, or any active or uncontrolled infections
* Patients with anti-HBV core antibodies (past infection with HBV) but who are negative for Hepatitis B Virus Surface Antigen (HBVsAg) (either anti-HBS Ab positive or negative) and are positive for HBV- Deoxyribonucleic acid (DNA) by Polymerase chain reaction (PCR) analysis
* Concomitant diseases requiring chronic steroid administration
* Active second malignancy within the 2 years prior to study (except for non-melanoma skin cancer and in situ cervix or breast or prostate carcinoma)
* Eastern Cooperative Oncology Group (ECOG) performance status \>/= 3

Primary outcomes:
measure: Overall Response Rate
timeFrame: Up to 42 months
Secondary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 53 months
measure: Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations
timeFrame: Up to 53 months
measure: Hospitalization Days
timeFrame: Up to 53 months
measure: Progression-free Survival (PFS)
timeFrame: Up to 53 months
measure: Quality of Life (QoL): Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire
timeFrame: [Visit 1 (Screening, Week 0), at Visits 11 (Week 45) and 14 (Week 80) and at the end of the study (Month 42)]
Other outcomes:
Locations:
city: Afula
country: Israel
facility: Haemek Medical Center; Hematology Department
city: Beer Sheva
country: Israel
facility: Soroka Medical Center; Hematology Deptartment
city: Haifa
country: Israel
facility: Rambam Medical Center; Heamatology & Bone Marrow Transplantation
city: Haifa
country: Israel
facility: Bnei-Zion Medical Center; Hematology Dept
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center; Hematology Dept.
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Hospital; Haematology
city: Kfar Saba
country: Israel
facility: Meir Medical Center; Internal Dept A
city: Nahariya
country: Israel
facility: Western Galilee Hospital - Nahariya
city: Petach Tikva
country: Israel
facility: Beilinson Medical Center; Haematology
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Rishon Lezion
country: Israel
facility: ASSAF Harofe; Department of Hematology
city: Tel Aviv
country: Israel
facility: Ichilov Sourasky Medical Center; Heamatology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: