Rituximab or Zevalin - Efficacy Trial of Therapeutic Alternatives (RoZetta)

This study has been terminated.
(Sponsor decision)
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01662102
First received: August 3, 2012
Last updated: August 5, 2013
Last verified: August 2013
  Purpose

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 patients with follicular lymphoma.


Condition Intervention Phase
Follicular Lymphoma
Drug: Zevalin
Drug: Rituximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Randomized Study in Previously Untreated Follicular Lymphoma Patients to Evaluate the Efficacy of Consolidation With Zevalin® Versus Maintenance Treatment With Rituximab After Initial Therapeutic Response to Rituximab Plus Chemotherapy

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Progression-free survival (PFS), defined as time from randomization to progression, relapse and/or death from any cause, or need for a new treatment regardless of reason.


Secondary Outcome Measures:
  • Complete Response Rate [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Complete Response (CR) rates post randomization

  • Event Free Survival [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    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).

  • Time to Progression (TTP) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    TTP is defined as the time from randomization to the first disease progression.

  • Time to Next Anti-Lymphoma Treatment (TTNLT) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    TTNLT is defined as the time from randomization to the first introduction of any new anti lymphoma regimen.

  • Time to Next Chemotherapy (TTNCT) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    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. Patients who respond to treatment and patients who are lost to follow-up will be censored at the visit on which the dosing of a new medication was evaluated.

  • Overall Survival (OS) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    OS is defined as the time from randomization to death from any cause. In living patients, survival time will be censored on the last date patients were known to be alive.

  • Overall Response Rate (ORR) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Tumor response will be evaluated according to Cheson criteria at the time of randomization and at the end of the 2-year maintenance/observation, post randomization. ORR is defined as the proportion of patients with a CR or a PR, and will be compared between treatment groups. Patients with no response evaluation (for any reason) will be considered as not evaluable (NE).

  • Transformation at First Progression [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Transformation rate at first progression, defined as the appearance of diffuse areas of large lymphoma cells within a tumor site.

  • Quality of Life (QoL) [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    QoL will be assessed through EORTC FACT-G and QLQ-[C]30 questionnaires, and will be compared at each specified time point between treatment arms.

  • Pharmacoeconomics (cost effectiveness analysis) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    A cost-effectiveness analysis will be done that compares the efficiency (cost/effectiveness unit) of consolidation treatment with 90Y-ibritumomab tiuxetan compared to maintenance treatment with rituximab. The analysis will be conducted according to a health economic analysis plan independent from this clinical study protocol.


Enrollment: 1
Study Start Date: September 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zevalin
90Y-Ibritumomab tiuxetan will be administered 8 to 12 weeks after the last chemotherapy infusion. Each patient randomized to this treatment group will 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). Patients with a pre-treatment platelet count between 100 and 149 x109/L will receive 0.3 mCi/Kg 90Y-ibritumomab tiuxetan.The 90Y ibritumomab tiuxetan regimen is as follows: Day 1 rituximab (250 mg/m2); Day 7,8, or 9 rituximab (250 mg/m2) followed by 90Y ibritumomab tiuxetan within 4 hours of the end of the rituximab infusion.
Drug: Zevalin
Group A: Response consolidation with a single dose of 90Y-ibritumomab tiuxetan (Zevalin®) 0.4 mCi/Kg - Maximum dose: 32 mCi given with 2 doses of rituximab followed by observation for 24 months;
Other Name: 90Y-ibritumomab tiuxetan (Zevalin)
Active Comparator: Rituximab
Patients will receive 375 mg/m2 of rituximab, administered by I.V. infusion every 8 weeks, starting 8 to 12 weeks after the last R-chemotherapy cycle.
Drug: Rituximab
Group B: Response maintenance with 375 mg/m2 of rituximab every 8 weeks for 24 months (12 infusions)
Other Name: Rituxan

Detailed Description:

This is an open-label, multicenter and randomized study. Patients will be registered after response induction (PR/CR) to R-chemotherapy. Patients achieving either a PR or CR following R-chemotherapy will be 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 will be followed for 5 years.

This study is designed to be similar to the ZAR2007 study (EUDRACT No. 2007-006601-25) carried out by PETHEMA in Spain. It is expected that Spanish centers will contribute up to 230 patients; centers in the US and elsewhere will contribute the remaining 254 patients. The same randomization procedure will be used in both studies. The total sample size for the combined studies will be 484 randomized patients. Assuming that PFS will follow an exponential distribution with a constant hazard rate, with a 36 months uniform accrual period and an additional follow-up time of 60 months after the last patient is randomized, 242 patients per arm (484 total) will be necessary to observe 131 PFS events in the combined study.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 to 75 years of age
  • Previously untreated with histologically confirmed grade 1, 2 or 3a 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 R-CHOP (6 cycles of R-CHOP21 or R-CHOP14), R-CVP (6 cycles), or R-B (4 to 6 cycles).
  • Must have completed all doses of the induction treatment, except for the modifications allowed in the protocol.

Exclusion Criteria:

  • Transformation to high grade lymphoma (secondary to "low grade" FL)
  • Grade 3b follicular lymphoma
  • Primary follicular lymphoma of the skin or gastrointestinal tract
  • Previous treatment of follicular lymphoma
  • Altered renal and hepatic function
  • Known HIV infection and/or active HBV and/or HCV infection
  • Serious co-morbid conditions (for example, ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease).
  • Life expectancy < 6
  • Must have:

    • Platelet count ≥ 100x109/L
    • Bone marrow infiltration <25%
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01662102

Locations
United States, Arizona
21st Century Oncology
Sun City, Arizona, United States, 85351
United States, Georgia
Northeast Georgia Cancer Care
Athens, Georgia, United States, 30607
United States, Illinois
Illinois Cancer Specialists
Niles, Illinois, United States, 60714
United States, Minnesota
Park Nicollet Institute
St. Louis Park, Minnesota, United States, 55426
United States, West Virginia
Charleston Area Medical Center
Charleston, West Virginia, United States, 25304
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
Principal Investigator: Fernando Cabanillas, MD M.D. Anderson Cancer Center
Principal Investigator: Thomas Witzig, MD The Mayo Clinic & Foundation
Principal Investigator: Steven E Finkelstein, MD 21st Century Oncology
Principal Investigator: Leonard Klein, MD Illinois Cancer Specialists - US Oncology
Principal Investigator: Steven Jubelirer, MD West Virginia University
Principal Investigator: Petros Nikolinakos, MD Northeast Georgia Cancer Care
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01662102     History of Changes
Other Study ID Numbers: SPI-ZEV-12-302
Study First Received: August 3, 2012
Last Updated: August 5, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Follicular
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on October 19, 2014