Rituximab or Zevalin - Efficacy Trial of Therapeutic Alternatives (RoZetta)
- Registration Number
- NCT01662102
- Lead Sponsor
- Spectrum Pharmaceuticals, Inc
- Brief Summary
The purpose of this study is to evaluate the effect of consolidation treatment Zevalin® versus maintenance treatment with Rituxan® on progression-free survival (PFS) following response induction with chemotherapy plus rituximab in previously untreated participants with follicular lymphoma.
- Detailed Description
This is an open-label, multicenter and randomized study. Participants registered after response induction (PR/CR) to R-chemotherapy. Participants achieving either a partial response (PR) or complete response (CR) following R-chemotherapy eligible for randomization to either consolidation with 90Y-ibritumumab tiuxetan followed by observation for 24 months, or rituximab maintenance for 24 months. After the observation/maintenance period, patients follow up for 5 years.
This study was terminated early for business reasons. (Maximum duration of study was up to approximately 2.7 months).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1
- 18 to 75 years of age.
- Previously untreated with histologically confirmed grade 1, 2 or 3a cluster of differentiation-20 (CD20)-positive follicular lymphoma, with any of the GELF (Groupe d'Etude de Lymphomes Folliculaires) treatment criteria prior to induction.
- Achieved a response to induction treatment with either rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (6 cycles of R-CHOP21 or R-CHOP14), rituximab-cyclophosphamide, vincristine and prednisone (R-CVP) (6 cycles), or rituximab-bendamustine (R-B) (4 to 6 cycles).
- Must have completed all doses of the induction treatment, except for the modifications allowed in the protocol.
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Transformation to high grade lymphoma (secondary to "low grade" follicular lymphoma [FL]).
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Grade 3b follicular lymphoma.
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Primary follicular lymphoma of the skin or gastrointestinal tract.
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Previous treatment of follicular lymphoma.
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Altered renal and hepatic function.
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Known human immunodeficiency virus (HIV) infection and/or active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection
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Serious co-morbid conditions (for example, ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease).
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Life expectancy < 6.
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Must have:
- Platelet count ≥ 100x10^9/L.
- Bone marrow infiltration <25%.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Zevalin Regimen Consolidation (Group A) Zevalin 90Y-Ibritumomab tiuxetan administered 8 to 12 weeks after the last chemotherapy infusion. Each participant randomized to this treatment group was to receive a therapeutic dose of 14.8 MBq/kg (0.4 mCi/kg of total body weight) of 90Y ibritumomab tiuxetan (maximum 1,184 MBq or 32 mCi). Participants with a pre-treatment platelet count between 100 and 149 x10\^9/L were to receive 0.3 mCi/Kg 90Y-ibritumomab tiuxetan. (Body weight ≤80 kg: 14.8 MBq \[0.4 mCi\] yttrium-90/kg and Body weight \>80 kg: 1,184 MBq \[32 mCi\] maximum dose). The 90Y ibritumomab tiuxetan regimen is as follows: Day 1 rituximab (250 mg/m\^2); Day 7,8, or 9 rituximab (250 mg/m\^2) followed by 90Y ibritumomab tiuxetan within 4 hours of the end of the rituximab infusion. (Maximum duration of study was up to approximately 2.7 months). Zevalin Regimen Consolidation (Group A) Rituximab 90Y-Ibritumomab tiuxetan administered 8 to 12 weeks after the last chemotherapy infusion. Each participant randomized to this treatment group was to receive a therapeutic dose of 14.8 MBq/kg (0.4 mCi/kg of total body weight) of 90Y ibritumomab tiuxetan (maximum 1,184 MBq or 32 mCi). Participants with a pre-treatment platelet count between 100 and 149 x10\^9/L were to receive 0.3 mCi/Kg 90Y-ibritumomab tiuxetan. (Body weight ≤80 kg: 14.8 MBq \[0.4 mCi\] yttrium-90/kg and Body weight \>80 kg: 1,184 MBq \[32 mCi\] maximum dose). The 90Y ibritumomab tiuxetan regimen is as follows: Day 1 rituximab (250 mg/m\^2); Day 7,8, or 9 rituximab (250 mg/m\^2) followed by 90Y ibritumomab tiuxetan within 4 hours of the end of the rituximab infusion. (Maximum duration of study was up to approximately 2.7 months). Rituximab Maintenance (Group B) Rituximab Participants were to receive 375 mg/m\^2 of rituximab, administered by intravenous (I.V.) infusion every 8 weeks, starting 8 to 12 weeks after the last R-chemotherapy cycle. (Maximum duration of study was up to approximately 2.7 months).
- Primary Outcome Measures
Name Time Method Progression Free Survival Up to approximately 2.7 months Progression-free survival (PFS) is defined as the time from randomization until progression, relapse, death from any cause, or introduction of a new anti-lymphoma treatment (chemotherapy, radiation therapy or immunotherapy).
- Secondary Outcome Measures
Name Time Method Time to Progression (TTP) Up to approximately 2.7 months TTP is defined as the time from randomization to the first disease progression.
Transformation at First Progression Up to approximately 2.7 months Transformation rate at first progression, defined as the appearance of diffuse areas of large lymphoma cells within a tumor site.
Number of Participants With Secondary Malignancies Up to approximately 2.7 months Functional Assessment of Cancer - General (FACT-G) Up to approximately 2.7 months The FACT-G is a participant rated, 27-item compilation of general questions divided into 4 primary Quality of Life (QOL) sub-scales: physical well-being (PWB; 7-items, score range 0-28), social/family well-being (SWB; 7-items, score range 0-28), emotional well-being (EWB; 6-items, score range 0-24), and functional well-being (FWB; 7-items, score range 0-28). This tool represents the generic core questionnaire that are utilized in combination with cancer site-specific questionnaires, (FBrain, in this study) Overall score and four subscale scores with ranges and distributions that are sample-specific can be calculated.FACT-G is scored by summing the individual scale scores; higher scores indicate better quality of life. FACT-G uses 5-point rating scale ranging from (0) = Not at all; (1) = A little bit; (2) = Somewhat; (3) = Quite a bit; to (4) = Very much.The FACT-G total score is the sum of the four subscale scores (if least 80% completed) and has a possible range of 0-108 points.
Pharmacoeconomics (Cost Effectiveness Analysis) Up to approximately 2.7 months A cost-effectiveness analysis done that compares the efficiency (cost/effectiveness unit) of consolidation treatment with 90Y-ibritumomab tiuxetan compared to maintenance treatment with rituximab. The analysis conducted according to a health economic analysis plan independent from this clinical study protocol.
Time to Next Anti-Lymphoma Treatment (TTNLT) Up to approximately 2.7 months TTNLT is defined as the time from randomization to the first introduction of any new anti lymphoma regimen.
Overall Response Rate (ORR) Up to approximately 2.7 months Tumor response evaluated according to Cheson criteria at the time of randomization and at the end of the maintenance/observation, post randomization. ORR is defined as the percentage of Participants with a complete response (CR) or a partial response (PR), and compared between treatment groups. Participants with no response evaluation (for any reason) considered as not evaluable (NE).
Number of Participants With Toxicity Up to approximately 2.7 months Toxicity graded according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0.
Complete Response Rate Up to approximately 2.7 months European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Up to approximately 2.7 months EORTC-QLQ-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. First 28 questions used 4-point scale (1=not at all,2=a little,3=quite a bit,4=very much) for evaluating 5 functional scales (physical,role,emotional,cognitive,social), 3 symptom scales (fatigue,nausea/vomiting,pain) \& other single items. For each item,high score represented high level of symptomatology/problem. Last 2 questions represented participant's assessment of overall health \& quality of life, coded on 7-point scale (1=very poor to 7=excellent).EORTC QLQ-C30 observed values and change from baseline for global health status (scoring of questions 29 \& 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Answers were converted into grading scale, with values between 0 and 100. High score represented a favourable outcome with a best quality of life for participant.
Event Free Survival Up to approximately 2.7 months EFS time is defined as the time from randomization to first documented progression, death from any cause, or introduction of a new anti-lymphoma treatment (chemotherapy, radiotherapy or immunotherapy).
Overall Survival (OS) Up to approximately 2.7 months OS is defined as the time from randomization to death from any cause. In living patients, survival time was censored on the last date participants were known to be alive.
Time to Next Chemotherapy (TTNCT) Up to approximately 2.7 months TTNCT is defined as the time from randomization to the first introduction of any new chemotherapy (cytotoxic or radioimmunotherapy). The TTNCT may be the same as the TTNLT. Participants who respond to treatment and Participants who are lost to follow-up censored at the visit on which the dosing of a new medication was evaluated.
Trial Locations
- Locations (5)
Charleston Area Medical Center
🇺🇸Charleston, West Virginia, United States
Park Nicollet Institute
🇺🇸Saint Louis Park, Minnesota, United States
Northeast Georgia Cancer Care
🇺🇸Athens, Georgia, United States
21st Century Oncology
🇺🇸Sun City, Arizona, United States
Illinois Cancer Specialists
🇺🇸Niles, Illinois, United States