Trial Outcomes & Findings for A Study of Rituximab (MabThera) in Participants With Chronic Lymphocytic Leukemia (CLL) (NCT NCT02533401)
NCT ID: NCT02533401
Last Updated: 2016-05-02
Results Overview
Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: greater than or equal to (≥) 50 percent (%) increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 centimeters (cm) from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. The percentage of participants with death or documented disease progression at any time during the study was calculated.
COMPLETED
PHASE2
34 participants
Up to 5 years (from Baseline until disease progression or death, whichever occurred first)
2016-05-02
Participant Flow
Participant milestones
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via intravenous (IV) infusion as 375 milligrams per meter-squared (mg/m\^2) on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.
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|---|---|
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Overall Study
STARTED
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34
|
|
Overall Study
COMPLETED
|
23
|
|
Overall Study
NOT COMPLETED
|
11
|
Reasons for withdrawal
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via intravenous (IV) infusion as 375 milligrams per meter-squared (mg/m\^2) on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.
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|---|---|
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Overall Study
Adverse Event/Intercurrent Disease
|
3
|
|
Overall Study
Death
|
5
|
|
Overall Study
Insufficient Response/Progressed Disease
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Violation of Selection Criteria
|
1
|
Baseline Characteristics
A Study of Rituximab (MabThera) in Participants With Chronic Lymphocytic Leukemia (CLL)
Baseline characteristics by cohort
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=34 Participants
Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via IV infusion as 375 mg/m\^2 on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.
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|---|---|
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Age, Continuous
|
60.3 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Sex: Female, Male
Female
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5 Participants
n=5 Participants
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Sex: Female, Male
Male
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29 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 5 years (from Baseline until disease progression or death, whichever occurred first)Population: All Participants Enrolled.
Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: greater than or equal to (≥) 50 percent (%) increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 centimeters (cm) from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. The percentage of participants with death or documented disease progression at any time during the study was calculated.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=34 Participants
Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via IV infusion as 375 mg/m\^2 on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.
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|---|---|
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Percentage of Participants With Death or Disease Progression
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24 percentage of participants
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PRIMARY outcome
Timeframe: Up to 5 years (from Baseline until disease progression or death, whichever occurred first)Population: All Participants Enrolled.
Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: ≥50% increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 cm from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. PFS was defined as the time from study inclusion until first event of disease progression or death and was estimated using Kaplan-Meier analysis.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=34 Participants
Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via IV infusion as 375 mg/m\^2 on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.
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|---|---|
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Progression-Free Survival (PFS)
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47.2 months
Interval 42.2 to 52.2
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PRIMARY outcome
Timeframe: Up to 5 years (from Baseline until death)Population: All Participants Enrolled.
Participants were followed for survival throughout the study. The percentage of participants who died of any cause during the study was calculated.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=34 Participants
Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via IV infusion as 375 mg/m\^2 on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.
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|---|---|
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Percentage of Participants Who Died
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14 percentage of participants
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PRIMARY outcome
Timeframe: Up to 5 years (from Baseline until death)Population: All Participants Enrolled.
Participants were followed for survival throughout the study. OS was defined as the time from study inclusion until death from any cause and was estimated using Kaplan-Meier analysis
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=34 Participants
Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via IV infusion as 375 mg/m\^2 on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.
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|---|---|
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Overall Survival (OS)
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49.5 months
Interval 44.8 to 54.2
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PRIMARY outcome
Timeframe: Up to 4 years (assessed every 3 months during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up)Population: All Participants Enrolled.
Treatment response was monitored throughout the study and assessed using standardized criteria. CR was defined as hemoglobin ≥11 grams per deciliter (g/dL), lymphocytes less than (\<) 4000 cells per cubic millimeter (cells/mm\^3), neutrophils greater than (\>) 1500 cells/mm\^3, platelets \>100,000 cells/mm\^3, bone marrow (BM) biopsy with \<30% lymphocytes with no lymphocytic infiltrates, no evidence of lymphoid nodules on physical exam, and performance status of 0. PR was defined as \>50% decrease in size of enlarged lymph nodes, hepatomegaly, and splenomegaly, with peripheral counts meeting the same criteria as CR or ≥50% improvement from pre-treatment values. Participants with lymphoid nodules on BM biopsy who otherwise met CR criteria were considered nPR. The percentage of participants with each level of best overall response was calculated.
Outcome measures
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=34 Participants
Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via IV infusion as 375 mg/m\^2 on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.
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|---|---|
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Percentage of Participants With Complete Response (CR), Nodular Partial Response (nPR), or Partial Response (PR)
CR
|
71 percentage of participants
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Percentage of Participants With Complete Response (CR), Nodular Partial Response (nPR), or Partial Response (PR)
nPR
|
9 percentage of participants
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Percentage of Participants With Complete Response (CR), Nodular Partial Response (nPR), or Partial Response (PR)
PR
|
18 percentage of participants
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Adverse Events
Rituximab + Fludarabine + Cyclophosphamide
Serious adverse events
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=34 participants at risk
Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via IV infusion as 375 mg/m\^2 on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.
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|---|---|
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Blood and lymphatic system disorders
Anemia
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2.9%
1/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
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|
Blood and lymphatic system disorders
Neutropenia
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14.7%
5/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Gastrointestinal disorders
Abdominal pain
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2.9%
1/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
General disorders
Death
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2.9%
1/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
General disorders
Fever
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8.8%
3/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
General disorders
Infusion related reaction
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2.9%
1/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Infections and infestations
Febrile neutropenia
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20.6%
7/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Infections and infestations
Bronchial infection
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2.9%
1/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Infections and infestations
Sepsis
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2.9%
1/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm (colon)
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2.9%
1/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Nervous system disorders
Seizure
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2.9%
1/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
2.9%
1/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Surgical and medical procedures
Surgical and medical procedures (gallbladder)
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2.9%
1/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
Other adverse events
| Measure |
Rituximab + Fludarabine + Cyclophosphamide
n=34 participants at risk
Participants with CLL received 6 treatment cycles of chemotherapy. Rituximab was administered via IV infusion as 375 mg/m\^2 on Day 1 of Cycle 1 and as 500 mg/m\^2 on Day 1 of Cycles 2 to 6. Fludarabine was given as 25 mg/m\^2 daily and cyclophosphamide as 250 mg/m\^2 daily, each via IV infusion on Days 2 to 4 during Cycle 1 and on Days 1 to 3 during Cycles 2 to 6. The length of each cycle was 28 days.
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|---|---|
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Blood and lymphatic system disorders
Anemia
|
23.5%
8/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Blood and lymphatic system disorders
Leukopenia
|
17.6%
6/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Blood and lymphatic system disorders
Low platelets
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29.4%
10/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Blood and lymphatic system disorders
Hypogammaglobulinemia
|
17.6%
6/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
|
Infections and infestations
Skin infection
|
20.6%
7/34 • Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up
|
Additional Information
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