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

Lymphocytic Leukemia, Chronic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01263704
• Other study ID #: ML25464
• Status: Completed
• Phase: Phase 2
• First received: December 17, 2010
• Last updated: April 18, 2018
• Start date: July 17, 2011
• Est. completion date: April 3, 2017

Study information

• Verified date: April 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: April 3, 2017
• Est. primary completion date: April 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Cyclophosphamide
150 milligrams per square meter (mg/m^2) intravenously (IV) on Days 1-3 of each 28-day cycle for 6 cycles
• Fludarabine
12.5 mg/m^2 IV on Days 1-3 of every 28-day cycle for 6 cycles
• Rituximab
375 mg/m^2 IV Day 0 of Cycle 1, 500 mg/m^2 IV Day 1 of Cycles 2-6. Each cycle was 28 days.

Locations

Country	Name	City	State
Israel	Haemek Medical Center; Hematology Department	Afula
Israel	Soroka Medical Center; Hematology Deptartment	Beer Sheva
Israel	Bnei-Zion Medical Center; Hematology Dept	Haifa
Israel	Rambam Medical Center; Heamatology & Bone Marrow Transplantation	Haifa
Israel	Hadassah Ein Karem Hospital; Haematology	Jerusalem
Israel	Shaare Zedek Medical Center; Hematology Dept.	Jerusalem
Israel	Meir Medical Center; Internal Dept A	Kfar Saba
Israel	Western Galilee Hospital - Nahariya	Nahariya
Israel	Beilinson Medical Center; Haematology	Petach Tikva
Israel	Kaplan Medical Center	Rehovot
Israel	ASSAF Harofe; Department of Hematology	Rishon Lezion
Israel	Ichilov Sourasky Medical Center; Heamatology	Tel Aviv

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 42 months
Secondary	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.	Up to 53 months
Secondary	Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations		Up to 53 months
Secondary	Hospitalization Days		Up to 53 months
Secondary	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.	Up to 53 months
Secondary	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.	[Visit 1 (Screening, Week 0), at Visits 11 (Week 45) and 14 (Week 80) and at the end of the study (Month 42)]