Trial Outcomes & Findings for A Study of MabThera/Rituxan (Rituximab) in Combination With Fludarabine And Cyclophosphamide as Primary Therapy in Elderly Patients With Chronic Lymphocytic Leukemia (NCT NCT01263704)

Last Updated: 2018-04-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

Up to 42 months

Results posted on

2018-04-23

Participant Flow

Participant milestones

Participant milestones
Measure	Rituximab Plus Fludarabine and Cyclophosphamide Elderly participants with chronic lymphocytic leukemia (CLL) received combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment was followed by a follow up period of 36 months.
Overall Study STARTED	42
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab Plus Fludarabine and Cyclophosphamide Elderly participants with chronic lymphocytic leukemia (CLL) received combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment was followed by a follow up period of 36 months.
Overall Study Progressive disease	18
Overall Study Adverse Event	3
Overall Study Death	2
Overall Study Patient withdrew consent	2
Overall Study Eligibility criteria not fulfilled	1
Overall Study Lost to Follow-up	1
Overall Study Colon metastases	1
Overall Study Principal Investigator (PI) decision	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab Plus Fludarabine and Cyclophosphamide n=42 Participants Elderly participants with chronic lymphocytic leukemia (CLL) received combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment was followed by a follow up period of 36 months.
Age, Continuous	72.9 years STANDARD_DEVIATION 5.0 • n=42 Participants
Sex: Female, Male Female	13 Participants n=42 Participants
Sex: Female, Male Male	29 Participants n=42 Participants

PRIMARY outcome

Timeframe: Up to 42 months

Population: Efficacy analysis population included all participants who received rituximab during the study.

Outcome measures

Outcome measures
Measure	Rituximab Plus Fludarabine and Cyclophosphamide n=40 Participants Elderly participants with chronic lymphocytic leukemia (CLL) received combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment was followed by a follow up period of 36 months.
Overall Response Rate	67.5 percentage of participants Interval 50.9 to 81.4

SECONDARY outcome

Timeframe: Up to 53 months

Population: The safety population included all enrolled participants.

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.

Outcome measures

Outcome measures
Measure	Rituximab Plus Fludarabine and Cyclophosphamide n=42 Participants Elderly participants with chronic lymphocytic leukemia (CLL) received combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment was followed by a follow up period of 36 months.
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	97.6 percentage of participants
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	45.2 percentage of participants

SECONDARY outcome

Timeframe: Up to 53 months

Population: The safety population included all enrolled participants.

Outcome measures

Outcome measures
Measure	Rituximab Plus Fludarabine and Cyclophosphamide n=42 Participants Elderly participants with chronic lymphocytic leukemia (CLL) received combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment was followed by a follow up period of 36 months.
Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations Infection	47.6 percentage of participants
Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations Neutropenic fever	14.3 percentage of participants
Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations ≥ Grade 3 drug-related neutropenia	47.6 percentage of participants
Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations ≥ Grade 3 drug-related thrombocytopenia	11.9 percentage of participants
Percentage of Participants With Neutropenic Fever, Infection, >/= Grade 3 Drug-Related Neutropenia, >/= Grade 3 Drug-Related Thrombocytopenia, Hospitalizations Hospitalization	19.1 percentage of participants

SECONDARY outcome

Timeframe: Up to 53 months

Population: The safety population included all enrolled participants.

Outcome measures

Outcome measures
Measure	Rituximab Plus Fludarabine and Cyclophosphamide n=42 Participants Elderly participants with chronic lymphocytic leukemia (CLL) received combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment was followed by a follow up period of 36 months.
Hospitalization Days	8 days Interval 2.0 to 13.0

SECONDARY outcome

Timeframe: Up to 53 months

Population: Efficacy analysis population included all participants who received rituximab during the study.

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.

Outcome measures

Outcome measures
Measure	Rituximab Plus Fludarabine and Cyclophosphamide n=40 Participants Elderly participants with chronic lymphocytic leukemia (CLL) received combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment was followed by a follow up period of 36 months.
Progression-free Survival (PFS)	36.1 months Interval 27.3 to 48.1

SECONDARY outcome

Timeframe: [Visit 1 (Screening, Week 0), at Visits 11 (Week 45) and 14 (Week 80) and at the end of the study (Month 42)]

Population: Efficacy analysis population included all participants who received rituximab during the study. Participants from the efficacy analysis population, who completed the FACIT-F questionnaire at any time point during the study, were analyzed as indicated at each time point.

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.

Outcome measures

Outcome measures
Measure	Rituximab Plus Fludarabine and Cyclophosphamide n=40 Participants Elderly participants with chronic lymphocytic leukemia (CLL) received combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment was followed by a follow up period of 36 months.
Quality of Life (QoL): Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire Visit 1 (Screening, Week 0)	36.1 score on a scale Standard Deviation 11.1
Quality of Life (QoL): Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire Visit 11 (Week 45)	39.4 score on a scale Standard Deviation 9.2
Quality of Life (QoL): Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire Visit 14 (Week 80)	40.2 score on a scale Standard Deviation 10.1
Quality of Life (QoL): Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire End of the Study (Month 42)	47.0 score on a scale Standard Deviation 1.0

Adverse Events

Rituximab Plus Fludarabine and Cyclophosphamide

Serious events: 19 serious events

Other events: 41 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Rituximab Plus Fludarabine and Cyclophosphamide n=42 participants at risk Elderly participants with chronic lymphocytic leukemia (CLL) received combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment was followed by a follow up period of 36 months.
Blood and lymphatic system disorders Febrile neutropenia	14.3% 6/42 • Up to 53 months The safety population included all enrolled participants.
Blood and lymphatic system disorders Leukopenia	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Blood and lymphatic system disorders Thrombocytopenia	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Endocrine disorders Diabetes mellitus	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Gastrointestinal disorders Pancreatitis acute	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
General disorders Chills	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
General disorders Pyrexia	7.1% 3/42 • Up to 53 months The safety population included all enrolled participants.
Infections and infestations Herpes zoster	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Infections and infestations Pneumonia	7.1% 3/42 • Up to 53 months The safety population included all enrolled participants.
Infections and infestations Pneumonia bacterial	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Infections and infestations Sepsis	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Infections and infestations Subacute endocarditis	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Infections and infestations Urinary tract infection	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Injury, poisoning and procedural complications Compression fracture	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Injury, poisoning and procedural complications Femoral neck fracture	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Psychiatric disorders Delirium	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.4% 1/42 • Up to 53 months The safety population included all enrolled participants.

Other adverse events

Other adverse events
Measure	Rituximab Plus Fludarabine and Cyclophosphamide n=42 participants at risk Elderly participants with chronic lymphocytic leukemia (CLL) received combination treatment with low-dose fludarabine and cyclophosphamide combined with standard-dose of rituximab for 6 months. Treatment was followed by a follow up period of 36 months.
Blood and lymphatic system disorders Anemia	33.3% 14/42 • Up to 53 months The safety population included all enrolled participants.
Blood and lymphatic system disorders Leukopenia	9.5% 4/42 • Up to 53 months The safety population included all enrolled participants.
Blood and lymphatic system disorders Neutropenia	52.4% 22/42 • Up to 53 months The safety population included all enrolled participants.
Blood and lymphatic system disorders Thrombocytopenia	23.8% 10/42 • Up to 53 months The safety population included all enrolled participants.
Gastrointestinal disorders Constipation	16.7% 7/42 • Up to 53 months The safety population included all enrolled participants.
Gastrointestinal disorders Diarrhea	16.7% 7/42 • Up to 53 months The safety population included all enrolled participants.
Gastrointestinal disorders Nausea	16.7% 7/42 • Up to 53 months The safety population included all enrolled participants.
General disorders Asthenia	19.0% 8/42 • Up to 53 months The safety population included all enrolled participants.
General disorders Chills	9.5% 4/42 • Up to 53 months The safety population included all enrolled participants.
General disorders Fatigue	9.5% 4/42 • Up to 53 months The safety population included all enrolled participants.
General disorders Infusion related reaction	11.9% 5/42 • Up to 53 months The safety population included all enrolled participants.
General disorders Edema peripheral	7.1% 3/42 • Up to 53 months The safety population included all enrolled participants.
General disorders Pyrexia	9.5% 4/42 • Up to 53 months The safety population included all enrolled participants.
Infections and infestations Pneumonia	11.9% 5/42 • Up to 53 months The safety population included all enrolled participants.
Infections and infestations Urinary tract infection	11.9% 5/42 • Up to 53 months The safety population included all enrolled participants.
Investigations Neutrophil count decreased	7.1% 3/42 • Up to 53 months The safety population included all enrolled participants.
Musculoskeletal and connective tissue disorders Back pain	9.5% 4/42 • Up to 53 months The safety population included all enrolled participants.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.1% 3/42 • Up to 53 months The safety population included all enrolled participants.
Respiratory, thoracic and mediastinal disorders Cough	23.8% 10/42 • Up to 53 months The safety population included all enrolled participants.
Respiratory, thoracic and mediastinal disorders Dyspnea	7.1% 3/42 • Up to 53 months The safety population included all enrolled participants.
Skin and subcutaneous tissue disorders Pruritus	9.5% 4/42 • Up to 53 months The safety population included all enrolled participants.
Skin and subcutaneous tissue disorders Rash	14.3% 6/42 • Up to 53 months The safety population included all enrolled participants.

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