Back to resultsA Study of MabThera/Rituxan (Rituximab) in Combination With Fludarabine And Cyclophosphamide as Primary Therapy in Elderly Patients With Chronic Lymphocytic Leukemia
Primary Purpose
Lymphocytic Leukemia, Chronic
Status
Completed
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
Cyclophosphamide
Fludarabine
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Lymphocytic Leukemia, Chronic
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
Sites / Locations
- Haemek Medical Center; Hematology Department
- Soroka Medical Center; Hematology Deptartment
- Rambam Medical Center; Heamatology & Bone Marrow Transplantation
- Bnei-Zion Medical Center; Hematology Dept
- Shaare Zedek Medical Center; Hematology Dept.
- Hadassah Ein Karem Hospital; Haematology
- Meir Medical Center; Internal Dept A
- Western Galilee Hospital - Nahariya
- Beilinson Medical Center; Haematology
- Kaplan Medical Center
- ASSAF Harofe; Department of Hematology
- Ichilov Sourasky Medical Center; Heamatology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rituximab plus Fludarabine and Cyclophosphamide
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations
Hospitalization Days
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01263704
Brief Title
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
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
July 17, 2011 (Actual)
Primary Completion Date
April 3, 2017 (Actual)
Study Completion Date
April 3, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphocytic Leukemia, Chronic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rituximab plus Fludarabine and Cyclophosphamide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
150 milligrams per square meter (mg/m^2) intravenously (IV) on Days 1-3 of each 28-day cycle for 6 cycles
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
12.5 mg/m^2 IV on Days 1-3 of every 28-day cycle for 6 cycles
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
MabThera/Rituxan
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Response Rate
Description
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 Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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
Title
Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations
Time Frame
Up to 53 months
Title
Hospitalization Days
Time Frame
Up to 53 months
Title
Progression-free Survival (PFS)
Description
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
Title
Quality of Life (QoL): Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire
Description
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)]
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Haemek Medical Center; Hematology Department
City
Afula
ZIP/Postal Code
18101
Country
Israel
Facility Name
Soroka Medical Center; Hematology Deptartment
City
Beer Sheva
ZIP/Postal Code
8410101
Country
Israel
Facility Name
Rambam Medical Center; Heamatology & Bone Marrow Transplantation
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Bnei-Zion Medical Center; Hematology Dept
City
Haifa
ZIP/Postal Code
3339419
Country
Israel
Facility Name
Shaare Zedek Medical Center; Hematology Dept.
City
Jerusalem
ZIP/Postal Code
9103102
Country
Israel
Facility Name
Hadassah Ein Karem Hospital; Haematology
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Meir Medical Center; Internal Dept A
City
Kfar Saba
ZIP/Postal Code
44281
Country
Israel
Facility Name
Western Galilee Hospital - Nahariya
City
Nahariya
ZIP/Postal Code
22100
Country
Israel
Facility Name
Beilinson Medical Center; Haematology
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Kaplan Medical Center
City
Rehovot
ZIP/Postal Code
7661041
Country
Israel
Facility Name
ASSAF Harofe; Department of Hematology
City
Rishon Lezion
ZIP/Postal Code
70300
Country
Israel
Facility Name
Ichilov Sourasky Medical Center; Heamatology
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
12. IPD Sharing Statement
Learn more about this trial
A Study of MabThera/Rituxan (Rituximab) in Combination With Fludarabine And Cyclophosphamide as Primary Therapy in Elderly Patients With Chronic Lymphocytic Leukemia
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