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

Phase 2

Completed

• Conditions: Lymphocytic Leukemia, Chronic
• Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab

• Registration Number: NCT01263704
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2010-12-17
• Study First Submitted QC: 2010-12-17
• Study First Posted: 2010-12-21
• Study Start: 2011-07-17
• Primary Completion: 2017-04-03
• Study Completion: 2017-04-03
• Results First Submitted: 2018-03-19
• Status Verified: 2018-04
• Results First Submitted QC: 2018-04-18
• Last Update Submitted: 2018-04-18
• Results First Posted: 2018-04-23
• Last Update Posted: 2018-04-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rituximab plus Fludarabine and Cyclophosphamide	Fludarabine	Elderly participants with chronic lymphocytic leukemia (CLL) will receive combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment is followed by a follow up period of 36 months.
Rituximab plus Fludarabine and Cyclophosphamide	Cyclophosphamide	Elderly participants with chronic lymphocytic leukemia (CLL) will receive combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment is followed by a follow up period of 36 months.
Rituximab plus Fludarabine and Cyclophosphamide	Rituximab	Elderly participants with chronic lymphocytic leukemia (CLL) will receive combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment is followed by a follow up period of 36 months.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	Up to 42 months	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.

Secondary Outcome Measures

Name	Time	Method
Hospitalization Days	Up to 53 months
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to 53 months	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.
Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations	Up to 53 months
Progression-free Survival (PFS)	Up to 53 months	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.
Quality of Life (QoL): Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire	[Visit 1 (Screening, Week 0), at Visits 11 (Week 45) and 14 (Week 80) and at the end of the study (Month 42)]	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.

Trial Locations

Locations (12)

ASSAF Harofe; Department of Hematology; 🇮🇱 Rishon Lezion, Israel

Haemek Medical Center; Hematology Department; 🇮🇱 Afula, Israel

Hadassah Ein Karem Hospital; Haematology; 🇮🇱 Jerusalem, Israel

Soroka Medical Center; Hematology Deptartment; 🇮🇱 Beer Sheva, Israel

Bnei-Zion Medical Center; Hematology Dept; 🇮🇱 Haifa, 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

Ichilov Sourasky Medical Center; Heamatology; 🇮🇱 Tel Aviv, Israel

Rambam Medical Center; Heamatology & Bone Marrow Transplantation; 🇮🇱 Haifa, Israel