A Study of MabThera/Rituxan (Rituximab) in Combination With Fludarabine And Cyclophosphamide as Primary Therapy in Elderly Patients With Chronic Lymphocytic Leukemia

Hoffmann-La Roche42 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lymphocytic Leukemia, Chronic

Interventions

Eligibility

Sex: ALLMin age: 65 Years

Medical Language ↔ Plain English

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

Locations (12)

Haemek Medical Center; Hematology Department

Afula, Israel

Soroka Medical Center; Hematology Deptartment

Beersheba, Israel

Rambam Medical Center; Heamatology & Bone Marrow Transplantation

Haifa, Israel

Bnei-Zion Medical Center; Hematology Dept

Haifa, Israel

Shaare Zedek Medical Center; Hematology Dept.

Jerusalem, Israel

Hadassah Ein Karem Hospital; Haematology

Jerusalem, Israel

Meir Medical Center; Internal Dept A

Kfar Saba, Israel

Western Galilee Hospital - Nahariya

Nahariya, Israel

Beilinson Medical Center; Haematology

Petah Tikva, Israel

Kaplan Medical Center

Rehovot, Israel

...and 2 more locations

Outcomes

Primary Outcomes

Overall Response Rate

Overall response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) according to National Cancer Institute - Working Group \[NCI-WG\] guidelines. CR: no clonal B lymphocytes in peripheral blood, no significant lymphadenopathy, liver and spleen normal size, no disease symptoms, blood counts: absolute neutrophil count (ANC) \>1,500/microliter (mcL), platelets \> 100,000/mcL, hemoglobin \> 11.0 grams/deciliter (g/dL), normocellular bone marrow. PR: \>/= 50% decrease in clonal B lymphocyte count, \>/= 50% reduction in lymphadenopathy, \>/= 50% reduction of liver or spleen enlargement and ANC \>1,500/mcL, platelets \> 100,000/mcL, hemoglobin \> 11.0 g/dL OR \>/= 50% increase in ANC, platelets or hemoglobin.

Time frame: Up to 42 months

Secondary Outcomes

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. Preexisting conditions which worsen during a study are also considered as adverse events. An SAE is any experience that suggests a significant hazard, contraindication, side effect, or precaution, and fulfills any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.

Time frame: Up to 53 months

Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations

Time frame: Up to 53 months

Hospitalization Days

Time frame: Up to 53 months

Progression-free Survival (PFS)

PFS was defined as the interval from the first study drug treatment day to the first sign of disease progression according to NCI-WG guidelines. Progressive disease (PD): Any new lesion, any disease symptoms, \>/=50% increase in lymphadenopathy, splenomegaly, hepatomegaly, \>/= 50% increase in the number of circulating clonal B lymphocytes, decrease of hemoglobin levels by \> 2.0 g/dL, \>/= 50% decrease of platelet counts, increase of lymphocytes in bone marrow to more than 30% from normal.

Time frame: Up to 53 months

Quality of Life (QoL): Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire

The FACIT-F questionnaire consists of 13 questions with a total score range of 0 to 52 with 0 indicating a better outcome and 52 indicating a worse outcome.

Time frame: [Visit 1 (Screening, Week 0), at Visits 11 (Week 45) and 14 (Week 80) and at the end of the study (Month 42)]