Trial Outcomes & Findings for A Study of Rituximab (MabThera) in Combination With Chemotherapy in Participants With CD20-Positive B-Cell Chronic Lymphocytic Leukemia (NCT NCT01609023)

Last Updated: 2018-06-26

Results Overview

An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

Recruitment status

COMPLETED

Target enrollment

67 participants

Primary outcome timeframe

Baseline up to 24 months

Results posted on

2018-06-26

Participant Flow

Participant milestones

Participant milestones
Measure	Rituximab Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Overall Study STARTED	67
Overall Study COMPLETED	34
Overall Study NOT COMPLETED	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Overall Study Lack of Efficacy	3
Overall Study Withdrawal by Subject	4
Overall Study Lost to Follow-up	8
Overall Study Toxicity	3
Overall Study Disease progression	10
Overall Study Physician Decision	2
Overall Study Death	2
Overall Study Personal reasons	1

Baseline Characteristics

A Study of Rituximab (MabThera) in Combination With Chemotherapy in Participants With CD20-Positive B-Cell Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab n=67 Participants Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Age, Continuous	69.12 years STANDARD_DEVIATION 10.08 • n=99 Participants
Sex: Female, Male Female	25 Participants n=99 Participants
Sex: Female, Male Male	42 Participants n=99 Participants

PRIMARY outcome

Timeframe: Baseline up to 24 months

Population: Safety population included all eligible participants.

An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

Outcome measures

Outcome measures
Measure	Rituximab n=67 Participants Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Percentage of Participants With Adverse Events (AEs)	89.6 percentage of participants

SECONDARY outcome

Timeframe: From enrollment until disease progression or death, assessed up to 24 months

Population: ITT population

PFS was defined as the time from enrollment to the first documented progression of disease or death due to any cause. Progressive disease (PD) was defined as at least a 20 percent (%) increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. KaplanMeier estimate was used for analysis.

Outcome measures

Outcome measures
Measure	Rituximab n=67 Participants Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Progression-Free Survival (PFS) Assessed Using Local Standards	NA months Median PFS was not reached at the final follow up due to high number of censored participants.

SECONDARY outcome

Timeframe: Months 6, 12, 18, and 24

Population: ITT population. Here, 'Overall Number of Participants Analyzed' = number of participants who were evaluable for this outcome. 'Number Analyzed' = participants who were evaluable for specified timepoints.

PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Outcome measures
Measure	Rituximab n=67 Participants Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Percentage of Participants With Disease Progression or Death Assessed Using Local Standards Month 6	5.8 percentage of participants
Percentage of Participants With Disease Progression or Death Assessed Using Local Standards Month 12	11.1 percentage of participants
Percentage of Participants With Disease Progression or Death Assessed Using Local Standards Month 18	17.5 percentage of participants
Percentage of Participants With Disease Progression or Death Assessed Using Local Standards Month 24	14.7 percentage of participants

SECONDARY outcome

Timeframe: Months 6, 12, 18, and 24

Percentage of participants with CR or PR as determined by the investigator was reported. CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

Outcome measures

Outcome measures
Measure	Rituximab n=67 Participants Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) Assessed Using Local Standards Month 24	67.6 percentage of participants
Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) Assessed Using Local Standards Month 6	84 percentage of participants
Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) Assessed Using Local Standards Month 12	72.1 percentage of participants
Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) Assessed Using Local Standards Month 18	58.5 percentage of participants

SECONDARY outcome

Timeframe: Months 6, 12, 18, and 24

Percentage of participants with CR as determined by the investigator was reported. CR was defined as disappearance of all target lesions.

Outcome measures

Outcome measures
Measure	Rituximab n=67 Participants Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Percentage of Participants With CR Assessed Using Local Standards Month 6	42 percentage of participants
Percentage of Participants With CR Assessed Using Local Standards Month 12	41.8 percentage of participants
Percentage of Participants With CR Assessed Using Local Standards Month 18	37.5 percentage of participants
Percentage of Participants With CR Assessed Using Local Standards Month 24	44.1 percentage of participants

SECONDARY outcome

Timeframe: Months 6, 12, 18, and 24

Percentage of participants with PR as determined by the investigator was reported. PR was defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

Outcome measures

Outcome measures
Measure	Rituximab n=67 Participants Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Percentage of Participants With PR Assessed Using Local Standards Month 6	42 percentage of participants
Percentage of Participants With PR Assessed Using Local Standards Month 12	30.2 percentage of participants
Percentage of Participants With PR Assessed Using Local Standards Month 18	22.5 percentage of participants
Percentage of Participants With PR Assessed Using Local Standards Month 24	23.5 percentage of participants

SECONDARY outcome

Timeframe: From enrollment until disease progression or death, assessed up to 26 months

Population: ITT population

TTP is defined as the time from enrollment to the PD. PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Kaplan-Meier estimate was used for analysis.

Outcome measures

Outcome measures
Measure	Rituximab n=67 Participants Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Time to Progression (TTP) Assessed Using Local Standards	NA months Median TTP was not reached at the final follow up due to high number of censored participants

Adverse Events

Rituximab

Serious events: 33 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab n=67 participants at risk Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Blood and lymphatic system disorders Anaemia	4.5% 3/67 • Baseline up to 24 months Safety population
Blood and lymphatic system disorders Eosinophilia	1.5% 1/67 • Baseline up to 24 months Safety population
Blood and lymphatic system disorders Febrile neutropenia	7.5% 5/67 • Baseline up to 24 months Safety population
Blood and lymphatic system disorders Leukopenia	1.5% 1/67 • Baseline up to 24 months Safety population
Blood and lymphatic system disorders Neutropenia	14.9% 10/67 • Baseline up to 24 months Safety population
Blood and lymphatic system disorders Thrombocytopenia	4.5% 3/67 • Baseline up to 24 months Safety population
General disorders Asthenia	1.5% 1/67 • Baseline up to 24 months Safety population
General disorders Chest pain	1.5% 1/67 • Baseline up to 24 months Safety population
General disorders Death	1.5% 1/67 • Baseline up to 24 months Safety population
General disorders Disease progression	1.5% 1/67 • Baseline up to 24 months Safety population
General disorders Pyrexia	4.5% 3/67 • Baseline up to 24 months Safety population
Hepatobiliary disorders Drug-induced liver injury	1.5% 1/67 • Baseline up to 24 months Safety population
Immune system disorders Hypersensitivity	1.5% 1/67 • Baseline up to 24 months Safety population
Infections and infestations Bronchitis	1.5% 1/67 • Baseline up to 24 months Safety population
Infections and infestations Herpes zoster	3.0% 2/67 • Baseline up to 24 months Safety population
Infections and infestations Infection	1.5% 1/67 • Baseline up to 24 months Safety population
Infections and infestations Lung infection	1.5% 1/67 • Baseline up to 24 months Safety population
Infections and infestations Pneumonia	1.5% 1/67 • Baseline up to 24 months Safety population
Infections and infestations Respiratory tract infection	6.0% 4/67 • Baseline up to 24 months Safety population
Infections and infestations Sinusitis	1.5% 1/67 • Baseline up to 24 months Safety population
Infections and infestations Upper respiratory tract infection	3.0% 2/67 • Baseline up to 24 months Safety population
Injury, poisoning and procedural complications Femur fracture	1.5% 1/67 • Baseline up to 24 months Safety population
Injury, poisoning and procedural complications Rib fracture	1.5% 1/67 • Baseline up to 24 months Safety population
Investigations Blood creatinine increased	1.5% 1/67 • Baseline up to 24 months Safety population
Investigations Haemoglobin decreased	1.5% 1/67 • Baseline up to 24 months Safety population
Investigations Liver function test abnormal	1.5% 1/67 • Baseline up to 24 months Safety population
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.5% 1/67 • Baseline up to 24 months Safety population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.5% 1/67 • Baseline up to 24 months Safety population
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	1.5% 1/67 • Baseline up to 24 months Safety population
Nervous system disorders Dizziness	1.5% 1/67 • Baseline up to 24 months Safety population
Nervous system disorders Memory impairment	1.5% 1/67 • Baseline up to 24 months Safety population
Respiratory, thoracic and mediastinal disorders Asthma	1.5% 1/67 • Baseline up to 24 months Safety population
Surgical and medical procedures Spinal operation	1.5% 1/67 • Baseline up to 24 months Safety population

Other adverse events

Other adverse events
Measure	Rituximab n=67 participants at risk Participants with chronic lymphocytic leukemia treated with rituximab in combination with chemotherapy according to Summary of Product Characteristics (SPC) and routine clinical practice were observed for 24 months.
Blood and lymphatic system disorders Anaemia	14.9% 10/67 • Baseline up to 24 months Safety population
Blood and lymphatic system disorders Leukopenia	10.4% 7/67 • Baseline up to 24 months Safety population
Blood and lymphatic system disorders Neutropenia	50.7% 34/67 • Baseline up to 24 months Safety population
Blood and lymphatic system disorders Thrombocytopenia	17.9% 12/67 • Baseline up to 24 months Safety population
Gastrointestinal disorders Vomiting	7.5% 5/67 • Baseline up to 24 months Safety population
General disorders Chills	10.4% 7/67 • Baseline up to 24 months Safety population
General disorders Pyrexia	19.4% 13/67 • Baseline up to 24 months Safety population
Infections and infestations Respiratory tract infection	6.0% 4/67 • Baseline up to 24 months Safety population
Vascular disorders Hypertension	6.0% 4/67 • Baseline up to 24 months Safety population

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800-821-8590

Email: [email protected]

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