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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01263704
Recruitment Status : Completed
First Posted : December 21, 2010
Results First Posted : April 23, 2018
Last Update Posted : April 23, 2018
Information provided by (Responsible Party):
Hoffmann-La Roche

December 17, 2010
December 21, 2010
March 19, 2018
April 23, 2018
April 23, 2018
July 17, 2011
April 3, 2017   (Final data collection date for primary outcome measure)
Overall Response Rate [ Time Frame: 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.
Overall Response Rate (according to National Cancer Institute - Working Group [NCI-WG] guidelines) [ Time Frame: 5 years ]
Complete list of historical versions of study NCT01263704 on Archive Site
  • Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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 [ Time Frame: Up to 53 months ]
  • Hospitalization Days [ Time Frame: Up to 53 months ]
  • Progression-free Survival (PFS) [ Time Frame: 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 [ 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)] ]
    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.
  • Safety: Incidence of adverse events (especially neutropenic fever, infection rate, number of hospitalization days, thrombocytopenia >/= grade 3, neutropenia >/= grade 3)) [ Time Frame: 5 years ]
  • Progression-free survival (according to NCI-WG guidelines) [ Time Frame: up to 36 months ]
  • Time to next treatment [ Time Frame: up to 36 months ]
  • Quality of life: Functional Assessment of Chronic Illness Therapy (FACIT) questionnaire [ Time Frame: up to 36 months ]
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A Study of MabThera/Rituxan (Rituximab) in Combination With Fludarabine And Cyclophosphamide as Primary Therapy in Elderly Patients With Chronic Lymphocytic Leukemia
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
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.
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Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Lymphocytic Leukemia, Chronic
  • Drug: Cyclophosphamide
    150 milligrams per square meter (mg/m^2) intravenously (IV) on Days 1-3 of each 28-day cycle for 6 cycles
  • Drug: Fludarabine
    12.5 mg/m^2 IV on Days 1-3 of every 28-day cycle for 6 cycles
  • Drug: 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.
    Other Name: MabThera/Rituxan
Experimental: Rituximab plus Fludarabine and 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.
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
  • Drug: Rituximab
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
April 3, 2017
April 3, 2017   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
65 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
Not Provided
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
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
April 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP