Trial Outcomes & Findings for A Study of Rituximab in Combination With Fludarabine and Cyclophosphamide in Participants With Chronic Lymphocytic Leukemia and Favorable Somatic Status (NCT NCT01271010)

NCT ID: NCT01271010

Last Updated: 2018-03-20

Results Overview

Complete remission was defined as the disappearance of all signs of disease.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 89 participants
• Primary outcome timeframe: Up to approximately 5 years
• Results posted on: 2018-03-20

Participant Flow

Participant milestones

Measure	Rituximab + Fludarabine + Cyclophosphamide Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.
Overall Study STARTED	89
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	61

Reasons for withdrawal

Measure	Rituximab + Fludarabine + Cyclophosphamide Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.
Overall Study Reason not specified	11
Overall Study Start of new CLL therapy	1
Overall Study Protocol Violation	1
Overall Study Death	2
Overall Study Progression and relapse of disease	1
Overall Study Withdrawal by Subject	18
Overall Study Disease progression	27

Baseline Characteristics

A Study of Rituximab in Combination With Fludarabine and Cyclophosphamide in Participants With Chronic Lymphocytic Leukemia and Favorable Somatic Status

Baseline characteristics by cohort

Measure	Rituximab + Fludarabine + Cyclophosphamide n=89 Participants Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.
Age, Continuous	55.9 years STANDARD_DEVIATION 6.39 • n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: All enrolled participants who were evaluable for this outcome measure.

Complete remission was defined as the disappearance of all signs of disease.

Outcome measures

Measure

Rituximab + Fludarabine + Cyclophosphamide n=73 Participants Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.

Percentage of Participants With Complete Remission

49.3 percentage of participants

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: All enrolled participants who were evaluable for this outcome measure.

Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.

Outcome measures

Measure

Rituximab + Fludarabine + Cyclophosphamide n=73 Participants Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.

Percentage of Participants With Disease Progression

5.5 percentage of participants

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: All enrolled participants who were evaluable for this outcome measure.

Stable disease was defined as not meeting the criteria for partial remission or disease progression

Outcome measures

Measure

Rituximab + Fludarabine + Cyclophosphamide n=73 Participants Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.

Percentage of Participants With Stable Disease

4.1 percentage of participants

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: All enrolled participants who were evaluable for this outcome measure.

Partial remission was defined as a reduction in tumor size by >50%.

Outcome measures

Measure

Rituximab + Fludarabine + Cyclophosphamide n=73 Participants Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.

Percentage of Participants With Partial Remission

41.1 percentage of participants

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: Enrolled participants who were evaluable for this outcome measure.

Duration of Response was defined as the time period from the last day of study treatment to the day when disease progression occurred in participants who previously had complete or partial remission. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. Complete remission was defined as the disappearance of all signs of disease. Partial remission was defined as a reduction in tumor size by >50%.

Outcome measures

Measure

Rituximab + Fludarabine + Cyclophosphamide n=61 Participants Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.

Duration of Response

NA days Median of duration of response to treatment was not achieved.

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: Enrolled participants who were evaluable for this outcome measure.

Progression-free survival was defined as the time period from the first day of study treatment to the day when disease progression occurred. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.

Outcome measures

Measure

Rituximab + Fludarabine + Cyclophosphamide n=85 Participants Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.

Progression-free Survival

NA days Median of progression-free survival was not achieved.

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: Enrolled participants who were evaluable for this outcome measure.

Event-free survival was defined as the time period from the first day of study treatment to occurrence of any of the following events: appearance of disease progression or relapse; prescription of a new treatment for disease relapse; death caused by B-cell chronic lymphocytic leukemia (B-CLL); or complications from B-CLL or therapy. Relapse was defined as disease progression in participants with complete or partial remission lasting at least 6 months after treatment completion. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. Complete remission was defined as the disappearance of all signs of disease. Partial remission was defined as a reduction in tumor size by >50%.

Outcome measures

Measure

Rituximab + Fludarabine + Cyclophosphamide n=85 Participants Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.

Event-free Survival

1567 days Interval 1036.0 to The curve representing the upper confidence limit for the survivor function was above 0.75. Therefore, the upper confidence limit could not be estimated.

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: Enrolled participants who were evaluable for this outcome measure.

Overall survival was defined as the time period from the first day of study treatment to participant death.

Outcome measures

Measure

Rituximab + Fludarabine + Cyclophosphamide n=89 Participants Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.

Overall Survival

NA days Median and confidence intervals were not calculable due to the low number of events of death.

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: Enrolled participants who were evaluable for this outcome measure.

Phenotypic remission was considered achieved if a participant had a negative test for minimal residual disease. A negative test for minimal residual disease was defined as tumor cells ≤0.01% of the total number of peripheral leukocytes.

Outcome measures

Measure

Rituximab + Fludarabine + Cyclophosphamide n=63 Participants Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.

Percentage of Participants With Phenotypic Remission

66.7 percentage of participants

PRIMARY outcome

Timeframe: Up to approximately 5 years

Population: All enrolled participants.

An AE was defined as any unfavorable medical occurrence in a participant receiving a study drug, regardless of relationship the study drug. An AE was considered serious if it met any of the following criteria: was fatal or life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was clinically significant and/or required an intervention to prevent any of the listed criteria.

Outcome measures

Measure	Rituximab + Fludarabine + Cyclophosphamide n=89 Participants Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.
Percentage of Participants With Adverse Events (AEs) and Serious AEs Non-serious AEs	78.65 percentage of participants
Percentage of Participants With Adverse Events (AEs) and Serious AEs Serious AEs	13.48 percentage of participants

Adverse Events

Rituximab + Fludarabine + Cyclophosphamide

Serious events: 12 serious events

Other events: 70 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rituximab + Fludarabine + Cyclophosphamide n=89 participants at risk Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.
Infections and infestations Herpes zoster	2.2% 2/89 • Up to approximately 5 years
Infections and infestations Appendicitis	1.1% 1/89 • Up to approximately 5 years
Infections and infestations Peritonitis	1.1% 1/89 • Up to approximately 5 years
Infections and infestations Proctitis infectious	1.1% 1/89 • Up to approximately 5 years
Respiratory, thoracic and mediastinal disorders Pneumonia	2.2% 2/89 • Up to approximately 5 years
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	1.1% 1/89 • Up to approximately 5 years
Respiratory, thoracic and mediastinal disorders Squamous cell carcinoma of lung	1.1% 1/89 • Up to approximately 5 years
Blood and lymphatic system disorders Agranulocytosis	1.1% 1/89 • Up to approximately 5 years
Endocrine disorders Neuroendocrine tumour	1.1% 1/89 • Up to approximately 5 years
Gastrointestinal disorders Abdominal pain	1.1% 1/89 • Up to approximately 5 years
Gastrointestinal disorders Duodenal ulcer	1.1% 1/89 • Up to approximately 5 years
Injury, poisoning and procedural complications Brain contusion	1.1% 1/89 • Up to approximately 5 years
Injury, poisoning and procedural complications Injury	1.1% 1/89 • Up to approximately 5 years
Musculoskeletal and connective tissue disorders Contusion	1.1% 1/89 • Up to approximately 5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	1.1% 1/89 • Up to approximately 5 years
Pregnancy, puerperium and perinatal conditions Pregnancy	1.1% 1/89 • Up to approximately 5 years
Vascular disorders Duodenal ulcer haemorrhage	1.1% 1/89 • Up to approximately 5 years

Other adverse events

Measure	Rituximab + Fludarabine + Cyclophosphamide n=89 participants at risk Participants received rituximab 375 milligrams per square meter (mg/m\^2) intravenously (IV) on Day 1 of Cycle 1, then 500 mg/m\^2 IV on Day 1 of each subsequent cycle; fludarabine 25 mg/m\^2 IV or 40 mg/m\^2 orally on Days 1-3 of each cycle and cyclophosphamide 250 mg/m\^2 IV or 250 mg/m\^2 orally on Days 1-3 of each cycle. Treatment duration was 6 cycles, 28 days each.
Investigations Neutrophil count decreased	41.6% 37/89 • Up to approximately 5 years
Investigations White blood cell count decreased	22.5% 20/89 • Up to approximately 5 years
Blood and lymphatic system disorders Thrombocytopenia	11.2% 10/89 • Up to approximately 5 years
Blood and lymphatic system disorders Anaemia	10.1% 9/89 • Up to approximately 5 years
Blood and lymphatic system disorders Leukocytosis	5.6% 5/89 • Up to approximately 5 years
Infections and infestations Respiratory tract infection	9.0% 8/89 • Up to approximately 5 years
Gastrointestinal disorders Nausea	10.1% 9/89 • Up to approximately 5 years

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 1-800-821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER