Trial Outcomes & Findings for Rituximab Therapy in Follicular Lymphoma in Combination With Chemotherapy - REFLECT 1 (NCT NCT02461290)
NCT ID: NCT02461290
Last Updated: 2015-09-30
Results Overview
The safety and tolerability of rituximab was evaluated by collection of AEs, including clinically significant abnormalities and changes in laboratory data. An AE was defined as any untoward medical occurrence in a study participant regardless of the suspected cause. Serious AEs were those which, at any dose, met one or more of the following criteria: resulted in fatality, were life-threatening, necessitated new or prolonged existing hospitalization, produced persistent or significant disability, resulted in a congenital anomaly or birth defect, were considered medically significant, or required intervention to prevent any of the aforementioned outcomes. Those specific serious AEs which resulted in fatality were also reported separately.
Recruitment status
COMPLETED
Target enrollment
99 participants
Primary outcome timeframe
Up to 3 years (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
Results posted on
2015-09-30
Participant Flow
Participant milestones
| Measure |
Rituximab + Chemotherapy
Participants with Stage III or IV, previously untreated follicular lymphoma (FL) received rituximab in combination with chemotherapy, which was prescribed in accordance with local labeling and standard practice at the study site. Chemotherapy regimens included cyclophosphamide, vincristine, and prednisone (CVP); cyclophosphamide, doxorubin, vincristine, and predisone (CHOP); or fludarabine, cyclophosphamide, and mitoxantrone (FCM). Rituximab was administered as 375 milligrams per meter-squared (mg/m\^2) via intravenous (IV) infusion on Day 1 of each 21-day cycle for 8 cycles of induction therapy. Because the study was noninterventional, the rituximab regimen was also at the discretion of the prescribing physician.
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|---|---|
|
Overall Study
STARTED
|
99
|
|
Overall Study
COMPLETED
|
89
|
|
Overall Study
NOT COMPLETED
|
10
|
Reasons for withdrawal
| Measure |
Rituximab + Chemotherapy
Participants with Stage III or IV, previously untreated follicular lymphoma (FL) received rituximab in combination with chemotherapy, which was prescribed in accordance with local labeling and standard practice at the study site. Chemotherapy regimens included cyclophosphamide, vincristine, and prednisone (CVP); cyclophosphamide, doxorubin, vincristine, and predisone (CHOP); or fludarabine, cyclophosphamide, and mitoxantrone (FCM). Rituximab was administered as 375 milligrams per meter-squared (mg/m\^2) via intravenous (IV) infusion on Day 1 of each 21-day cycle for 8 cycles of induction therapy. Because the study was noninterventional, the rituximab regimen was also at the discretion of the prescribing physician.
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|---|---|
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Overall Study
Withdrawn for Inadequate Clinical Stage
|
7
|
|
Overall Study
Lost to Follow-up
|
3
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Baseline Characteristics
Rituximab Therapy in Follicular Lymphoma in Combination With Chemotherapy - REFLECT 1
Baseline characteristics by cohort
| Measure |
Rituximab + Chemotherapy
n=99 Participants
Participants with Stage III or IV, previously untreated FL received rituximab in combination with chemotherapy, which was prescribed in accordance with local labeling and standard practice at the study site. Chemotherapy regimens included CVP, CHOP, or FCM. Rituximab was administered as 375 mg/m\^2 via IV infusion on Day 1 of each 21-day cycle for 8 cycles of induction therapy. Because the study was noninterventional, the rituximab regimen was also at the discretion of the prescribing physician.
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|---|---|
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Age, Continuous
|
55.8 years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
|
Sex: Female, Male
Female
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56 Participants
n=5 Participants
|
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Sex: Female, Male
Male
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43 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 3 years (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)Population: ITT Population.
The safety and tolerability of rituximab was evaluated by collection of AEs, including clinically significant abnormalities and changes in laboratory data. An AE was defined as any untoward medical occurrence in a study participant regardless of the suspected cause. Serious AEs were those which, at any dose, met one or more of the following criteria: resulted in fatality, were life-threatening, necessitated new or prolonged existing hospitalization, produced persistent or significant disability, resulted in a congenital anomaly or birth defect, were considered medically significant, or required intervention to prevent any of the aforementioned outcomes. Those specific serious AEs which resulted in fatality were also reported separately.
Outcome measures
| Measure |
Rituximab + Chemotherapy
n=99 Participants
Participants with Stage III or IV, previously untreated FL received rituximab in combination with chemotherapy, which was prescribed in accordance with local labeling and standard practice at the study site. Chemotherapy regimens included CVP, CHOP, or FCM. Rituximab was administered as 375 mg/m\^2 via IV infusion on Day 1 of each 21-day cycle for 8 cycles of induction therapy. Because the study was noninterventional, the rituximab regimen was also at the discretion of the prescribing physician.
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|---|---|
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Number of Participants With an Adverse Event (AE), Serious AE, or Death Related to AE
Death related to AE
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7 participants
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Number of Participants With an Adverse Event (AE), Serious AE, or Death Related to AE
Any AE
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34 participants
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|
Number of Participants With an Adverse Event (AE), Serious AE, or Death Related to AE
Serious AE
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10 participants
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SECONDARY outcome
Timeframe: Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)Population: Data Analysis Population: All enrolled participants who provided complete and evaluable outcome data.
Tumor response was evaluated according to criteria published by Cheson et al (1999). According to consensus recommendations, CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. PR was defined as greater than or equal to (≥) 50 percent (%) decrease in sum of the products of greatest diameters (SPD) of the six largest dominant lymph nodes, no increase in size of other nodes, no increase in liver or spleen volume, a ≥50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease. The percentage of participants achieving CR or PR was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.
Outcome measures
| Measure |
Rituximab + Chemotherapy
n=86 Participants
Participants with Stage III or IV, previously untreated FL received rituximab in combination with chemotherapy, which was prescribed in accordance with local labeling and standard practice at the study site. Chemotherapy regimens included CVP, CHOP, or FCM. Rituximab was administered as 375 mg/m\^2 via IV infusion on Day 1 of each 21-day cycle for 8 cycles of induction therapy. Because the study was noninterventional, the rituximab regimen was also at the discretion of the prescribing physician.
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|---|---|
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Percentage of Participants With Complete Remission (CR) or Partial Remission (PR) According to International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL)
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73.2 percentage of participants
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SECONDARY outcome
Timeframe: Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)Population: Data Analysis Population.
Tumor response was evaluated according to criteria published by Cheson et al (1999). According to consensus recommendations, CR was defined as disappearance of all clinical/radiographic evidence of disease, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. The percentage of participants achieving CR was calculated as \[number of participants meeting the above criteria divided by the number analyzed\] multiplied by 100.
Outcome measures
| Measure |
Rituximab + Chemotherapy
n=86 Participants
Participants with Stage III or IV, previously untreated FL received rituximab in combination with chemotherapy, which was prescribed in accordance with local labeling and standard practice at the study site. Chemotherapy regimens included CVP, CHOP, or FCM. Rituximab was administered as 375 mg/m\^2 via IV infusion on Day 1 of each 21-day cycle for 8 cycles of induction therapy. Because the study was noninterventional, the rituximab regimen was also at the discretion of the prescribing physician.
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|---|---|
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Percentage of Participants With CR According to International Working Group Response Criteria for NHL
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61.6 percentage of participants
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SECONDARY outcome
Timeframe: At 1, 2, and 3 yearsPopulation: ITT Population.
Participants were followed for survival for up to 3 years. The overall survival rate at 1, 2, and 3 years was calculated as \[number of participants alive divided by the number analyzed\] multiplied by 100.
Outcome measures
| Measure |
Rituximab + Chemotherapy
n=99 Participants
Participants with Stage III or IV, previously untreated FL received rituximab in combination with chemotherapy, which was prescribed in accordance with local labeling and standard practice at the study site. Chemotherapy regimens included CVP, CHOP, or FCM. Rituximab was administered as 375 mg/m\^2 via IV infusion on Day 1 of each 21-day cycle for 8 cycles of induction therapy. Because the study was noninterventional, the rituximab regimen was also at the discretion of the prescribing physician.
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|---|---|
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Percentage of Participants Alive at 1, 2, and 3 Years
At 1 year
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94.2 percentage of participants
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Percentage of Participants Alive at 1, 2, and 3 Years
At 2 years
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92.6 percentage of participants
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Percentage of Participants Alive at 1, 2, and 3 Years
At 3 years
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92.6 percentage of participants
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Adverse Events
Rituximab + Chemotherapy
Serious events: 10 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rituximab + Chemotherapy
n=99 participants at risk
Participants with Stage III or IV, previously untreated FL received rituximab in combination with chemotherapy, which was prescribed in accordance with local labeling and standard practice at the study site. Chemotherapy regimens included CVP, CHOP, or FCM. Rituximab was administered as 375 mg/m\^2 via IV infusion on Day 1 of each 21-day cycle for 8 cycles of induction therapy. Because the study was noninterventional, the rituximab regimen was also at the discretion of the prescribing physician.
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|---|---|
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Infections and infestations
Encephalitis
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Infections and infestations
Septic shock
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Immune system disorders
Hypersensitivity
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2.0%
2/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
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Nervous system disorders
Cerebrovascular accident
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Nervous system disorders
Coma
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Nervous system disorders
Nervous system disorder
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Cardiac disorders
Cardiac arrest
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Vascular disorders
Thrombophlebitis
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Gastrointestinal disorders
Abdominal pain
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Hepatobiliary disorders
Hepatic failure
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
General disorders
Death
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
General disorders
Disease progression
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
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Other adverse events
| Measure |
Rituximab + Chemotherapy
n=99 participants at risk
Participants with Stage III or IV, previously untreated FL received rituximab in combination with chemotherapy, which was prescribed in accordance with local labeling and standard practice at the study site. Chemotherapy regimens included CVP, CHOP, or FCM. Rituximab was administered as 375 mg/m\^2 via IV infusion on Day 1 of each 21-day cycle for 8 cycles of induction therapy. Because the study was noninterventional, the rituximab regimen was also at the discretion of the prescribing physician.
|
|---|---|
|
Infections and infestations
Respiratory tract infection
|
3.0%
3/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Infections and infestations
Herpes simplex
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Blood and lymphatic system disorders
Neutropenia
|
17.2%
17/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Blood and lymphatic system disorders
Pancytopenia
|
4.0%
4/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Blood and lymphatic system disorders
Leucopenia
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12.1%
12/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Immune system disorders
Hypersensitivity
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4.0%
4/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Immune system disorders
Immunodeficiency
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1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Immune system disorders
Hypogammaglobulinaemia
|
1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Nervous system disorders
Paresthesia
|
6.1%
6/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
6.1%
6/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Gastrointestinal disorders
Nausea
|
8.1%
8/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Gastrointestinal disorders
Vomiting
|
1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Gastrointestinal disorders
Colitis
|
2.0%
2/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Hepatobiliary disorders
Hepatic lesion
|
1.0%
1/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
General disorders
Chills
|
9.1%
9/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
General disorders
Pyrexia
|
13.1%
13/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
7.1%
7/99 • Up to 18 months (at Screening, Baseline, end of induction therapy, and in accordance with routine practice)
ITT Population.
|
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