Lymphoma, Follicular
Conditions
Keywords
Sargramostim, Leukine, NHL
Brief summary
The purpose of this study is to evaluate whether treatment with rituximab plus sargramostim will be more effective than rituximab alone.
Detailed description
On 29 May 2009, Bayer began transitioning the sponsorship of this trial to Genzyme. As of 29 August 2009, Genzyme assumed responsibility for the close out of the study. NOTE: This study was originally posted by sponsor Berlex, Inc. Berlex, Inc. was renamed to Bayer HealthCare, Inc. The study was terminated early due to low enrollment; significant changes to the protocol would have been required to keep pace with the changing therapeutic landscape of indolent lymphoma.
Interventions
Sargramostim 250 μg, administered subcutaneously (SC) 3 times weekly for 8 weeks, beginning at least 1 hour before the first dose of rituximab
DRUGRituximab
Four doses of rituximab 375 mg/m2, administered intravenously (IV) once weekly for 4 weeks
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(abbreviated list): * Relapsed follicular B-cell lymphoma * One or more previous therapies for non-Hodgkin's * At least one measurable tumor by CT scan or MRI * Additional criteria to be determined at screening visit
Exclusion criteria
(abbreviated list): * Rituximab refractory (less than 6 months from last treatment with rituximab to relapse) * Currently receiving treatment for another cancer * Infection currently being treated * Active Hepatitis B * History of HIV infection * Pregnant * Additional criteria to be determined at screening visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Complete Response or Unconfirmed Complete Response at Week 8 With Confirmation at Week 12 | Week 8 (confirmed at Week 12) | Count of number of participants who responded with a Complete Response (complete disappearance of all detectable clinical and radiological evidence of disease) at week 8 and again clinically and radiologically confirmed at week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Treatment-Emergent Adverse Events (TEAE) | up to 12 weeks | Count of the number of participants who experienced treatment emergent adverse events (TEAEs). TEAEs occurred during the time study intervention was being taken occurring on or after Day 1 and no longer than 30 days after the last dose of study medication. |
| Participant Summary of Best Response Across All Visits | up to 24 months | Count of participants' best response within categories defined by the International Working Group (IWG): \> Complete Response (complete disappearance of detectable clinical and radiological evidence of disease), \> Complete Response Unconfirmed (unconfirmed complete disappearance), \> Partial Response (\>=50% decrease sum of the product of the greatest diameters in the six largest dominant nodes or nodal masses), \> Stable Disease (neither response nor disease progression), \> Progression (new lesion or increase by 50% of previously involved sites from nadir). |
| Kaplan-Meier Estimates of Progression-Free Survival | 24 months | Time to event was measured from the date of randomization to the date of first progressive disease (PD) or death. |
| Kaplan-Meier Estimates for Duration of Partial Response or Better to Treatment | 24 months | Count of days in which a participant experiences a Partial Response (\>=50% decrease sum of the product of the greatest diameters in the six largest dominant nodes or nodal masses) or better. Time to event was measured from the date of response to the date of progressive disease (PD) or death. |
| Summary of Cost Effectiveness | 24 months | A cost-effectiveness analysis from the payer perspective was to be performed. Only direct medical costs for each patient during the study period were to be included for analysis. Costs were to be calculated by multiplying each health care resource unit by the amount reimbursed by a payer. Health care resource utilization units are a way to normalize the quantity of health care provided to each participant so that costs can be compared. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
One hundred ninety-six (196) patients were planned and 44 centers were open for enrollment. Eighty-two (82) patients were screened from 22 investigator sites across the United States and Puerto Rico.
Pre-assignment details
82 patients screened
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Four doses of rituximab 375 mg/m2, administered intravenously (IV) once weekly for 4 weeks | 37 |
| Rituximab + Sargramostim Sargramostim 250 μg, administered subcutaneously (SC) 3 times weekly for 8 weeks, beginning at least 1 hour before the first dose of rituximab. Plus four doses of rituximab 375 mg/m2, administered intravenously (IV) once weekly for 4 weeks. | 38 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 4 | 3 |
| Overall Study | Progressive Disease | 19 | 21 |
| Overall Study | Study Closure | 11 | 12 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Rituximab | Rituximab + Sargramostim | Total |
|---|---|---|---|
| Age, Continuous | 61.5 years STANDARD_DEVIATION 10.23 | 59.4 years STANDARD_DEVIATION 8.68 | 60.5 years STANDARD_DEVIATION 9.47 |
| Race/Ethnicity, Customized Asian | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Black | 2 participants | 4 participants | 6 participants |
| Race/Ethnicity, Customized Caucasian | 26 participants | 29 participants | 55 participants |
| Race/Ethnicity, Customized Hispanic | 7 participants | 3 participants | 10 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 21 Participants | 18 Participants | 39 Participants |
| Sex: Female, Male Male | 16 Participants | 20 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 37 | 38 / 38 |
| serious Total, serious adverse events | 5 / 37 | 7 / 38 |
Outcome results
Primary
Number of Participants With a Complete Response or Unconfirmed Complete Response at Week 8 With Confirmation at Week 12
Count of number of participants who responded with a Complete Response (complete disappearance of all detectable clinical and radiological evidence of disease) at week 8 and again clinically and radiologically confirmed at week 12.
Time frame: Week 8 (confirmed at Week 12)
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab | Number of Participants With a Complete Response or Unconfirmed Complete Response at Week 8 With Confirmation at Week 12 | 1 participants |
| Rituximab + Sargramostim | Number of Participants With a Complete Response or Unconfirmed Complete Response at Week 8 With Confirmation at Week 12 | 3 participants |
p-value: 0.61822-sided Exact Conditional Test
Secondary
Kaplan-Meier Estimates for Duration of Partial Response or Better to Treatment
Count of days in which a participant experiences a Partial Response (\>=50% decrease sum of the product of the greatest diameters in the six largest dominant nodes or nodal masses) or better. Time to event was measured from the date of response to the date of progressive disease (PD) or death.
Time frame: 24 months
Population: Intent to treat population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab | Kaplan-Meier Estimates for Duration of Partial Response or Better to Treatment | 297.0 Days |
| Rituximab + Sargramostim | Kaplan-Meier Estimates for Duration of Partial Response or Better to Treatment | 396.0 Days |
Comparison: Log rank analysis is a comparison between treatment groups of the distribution of time to first progressive disease or death.p-value: 0.8217Log Rank
Secondary
Kaplan-Meier Estimates of Progression-Free Survival
Time to event was measured from the date of randomization to the date of first progressive disease (PD) or death.
Time frame: 24 months
Population: Intent to treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab | Kaplan-Meier Estimates of Progression-Free Survival | 361.0 Days |
| Rituximab + Sargramostim | Kaplan-Meier Estimates of Progression-Free Survival | 455.0 Days |
Comparison: Log rank analysis is a comparison between treatment groups of the distribution of time to first progressive disease or death.p-value: 0.5501Log Rank
Secondary
Participant Summary of Best Response Across All Visits
Count of participants' best response within categories defined by the International Working Group (IWG): \> Complete Response (complete disappearance of detectable clinical and radiological evidence of disease), \> Complete Response Unconfirmed (unconfirmed complete disappearance), \> Partial Response (\>=50% decrease sum of the product of the greatest diameters in the six largest dominant nodes or nodal masses), \> Stable Disease (neither response nor disease progression), \> Progression (new lesion or increase by 50% of previously involved sites from nadir).
Time frame: up to 24 months
Population: Intent to treat population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Participant Summary of Best Response Across All Visits | Complete Response | 5 participants |
| Rituximab | Participant Summary of Best Response Across All Visits | Complete Response Unconfirmed | 0 participants |
| Rituximab | Participant Summary of Best Response Across All Visits | Partial Response | 13 participants |
| Rituximab | Participant Summary of Best Response Across All Visits | Stable Disease | 11 participants |
| Rituximab | Participant Summary of Best Response Across All Visits | Progression | 4 participants |
| Rituximab | Participant Summary of Best Response Across All Visits | Unknown | 0 participants |
| Rituximab + Sargramostim | Participant Summary of Best Response Across All Visits | Progression | 3 participants |
| Rituximab + Sargramostim | Participant Summary of Best Response Across All Visits | Complete Response | 5 participants |
| Rituximab + Sargramostim | Participant Summary of Best Response Across All Visits | Stable Disease | 15 participants |
| Rituximab + Sargramostim | Participant Summary of Best Response Across All Visits | Complete Response Unconfirmed | 0 participants |
| Rituximab + Sargramostim | Participant Summary of Best Response Across All Visits | Unknown | 0 participants |
| Rituximab + Sargramostim | Participant Summary of Best Response Across All Visits | Partial Response | 14 participants |
Secondary
Summary of Cost Effectiveness
A cost-effectiveness analysis from the payer perspective was to be performed. Only direct medical costs for each patient during the study period were to be included for analysis. Costs were to be calculated by multiplying each health care resource unit by the amount reimbursed by a payer. Health care resource utilization units are a way to normalize the quantity of health care provided to each participant so that costs can be compared.
Time frame: 24 months
Population: No participants were analyzed because the study was terminated early due to low enrollment.
Secondary
Summary of Treatment-Emergent Adverse Events (TEAE)
Count of the number of participants who experienced treatment emergent adverse events (TEAEs). TEAEs occurred during the time study intervention was being taken occurring on or after Day 1 and no longer than 30 days after the last dose of study medication.
Time frame: up to 12 weeks
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab | Summary of Treatment-Emergent Adverse Events (TEAE) | Patients with Treatment-Related TEAEs | 21 participants |
| Rituximab | Summary of Treatment-Emergent Adverse Events (TEAE) | Patients with Serious TEAEs | 4 participants |
| Rituximab | Summary of Treatment-Emergent Adverse Events (TEAE) | Number of Deaths | 0 participants |
| Rituximab | Summary of Treatment-Emergent Adverse Events (TEAE) | Patients with Study Discontinuation due to TEAEs | 0 participants |
| Rituximab | Summary of Treatment-Emergent Adverse Events (TEAE) | Patients with TEAEs | 34 participants |
| Rituximab + Sargramostim | Summary of Treatment-Emergent Adverse Events (TEAE) | Patients with Study Discontinuation due to TEAEs | 2 participants |
| Rituximab + Sargramostim | Summary of Treatment-Emergent Adverse Events (TEAE) | Patients with TEAEs | 38 participants |
| Rituximab + Sargramostim | Summary of Treatment-Emergent Adverse Events (TEAE) | Patients with Treatment-Related TEAEs | 37 participants |
| Rituximab + Sargramostim | Summary of Treatment-Emergent Adverse Events (TEAE) | Number of Deaths | 0 participants |
| Rituximab + Sargramostim | Summary of Treatment-Emergent Adverse Events (TEAE) | Patients with Serious TEAEs | 4 participants |