Follicular Lymphoma
Conditions
Brief summary
This is a randomized, open-label, active-control, multicenter Phase 2 study of VELCADE+fludarabine in comparison with rituximab+fludarabine in subjects with relapsed advanced follicular lymphoma. Eligible subjects will be randomized in a 1:1 ratio between the 2 treatment arms (55 subjects per arm).
Interventions
DRUGrituximab
rituximab 375mg/m2 on Day 1 of every 35-day cycle
DRUGfludarabine
fludarabine 40mg/m2/day orally on Days 1 to 5 of every 35-day cycle
DRUGVELCADE
1.6 mg/m2 intravenously (IV) on Days 1, 8, 15, and 22 of every 35-day cycle
Sponsors
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Millennium Pharmaceuticals, Inc.
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
* Male or female subjects 18 years or older * Histologically proven diagnosis of follicular non-Hodgkin's lymphoma grades 1or 2 according to the World Health Organization classification * Subjects must have received at least 12 doses (375mg/m2 or appropriately adjusted dose) of rituximab for the treatment of this lymphoma as single agent rituximab or in rituximab-containing regimens as documented in the subject's medical record * Documented relapse or progression following last antineoplastic treatment * At least 1 measurable tumor mass (≥1.5 cm x ≥1.0 cm)
Exclusion criteria
* Subjects with histological or clinical transformation to an aggressive lymphoma * prior treatment with VELCADE or fludarabine. * antineoplastic (including unconjugated therapeutic antibodies), experimental, or radiation therapy within 3 weeks before randomization * nitrosoureas within 6 weeks before randomization * radioimmunoconjugates or toxin immunoconjugates within 10 weeks before randomization * major surgery within 3 weeks before randomization * chronic use of corticosteroids, such as dexamethasone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate | Up to 8 cycles (1 cycle is 35 days: 280 days) | The proportion of response-evaluable subjects who achieved a confirmed complete response (CR) or complete response unconfirmed (CRu). Disease response and progression were evaluated according to modified International Workshop Response Criteria (IWRC) criteria by radiographic imaging and other procedures as necessary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Up to 8 cycles (1 cycle is 35 days: 280 days) | The proportion of subjects who achieve CR, CRu, or partial response (PR) relative to the response evaluable population. Disease response and progression were evaluated according to the modified IWRC criteria by radiographic imaging and other procedures as necessary. |
Countries
France, Germany, Greece, Israel, Italy, Spain, Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Velcade + Fludarabine | 4 |
| Rituximab + Fludarabine | 8 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
Baseline characteristics
| Characteristic | Velcade + Fludarabine | Rituximab + Fludarabine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 6 Participants | 9 Participants |
| Age Continuous | 61.3 years STANDARD_DEVIATION 12.84 | 60.0 years STANDARD_DEVIATION 10.06 | 60.4 years STANDARD_DEVIATION 10.47 |
| Region of Enrollment France | 0 participants | 3 participants | 3 participants |
| Region of Enrollment Germany | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Greece | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Israel | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Italy | 1 participants | 3 participants | 4 participants |
| Region of Enrollment Spain | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Switzerland | 1 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 8 / 8 |
| serious Total, serious adverse events | 2 / 4 | 2 / 8 |
Outcome results
Primary
Complete Response Rate
The proportion of response-evaluable subjects who achieved a confirmed complete response (CR) or complete response unconfirmed (CRu). Disease response and progression were evaluated according to modified International Workshop Response Criteria (IWRC) criteria by radiographic imaging and other procedures as necessary.
Time frame: Up to 8 cycles (1 cycle is 35 days: 280 days)
Population: Received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Velcade + Fludarabine | Complete Response Rate | 2 participants |
| Rituximab + Fludarabine | Complete Response Rate | 3 participants |
Secondary
Overall Response Rate
The proportion of subjects who achieve CR, CRu, or partial response (PR) relative to the response evaluable population. Disease response and progression were evaluated according to the modified IWRC criteria by radiographic imaging and other procedures as necessary.
Time frame: Up to 8 cycles (1 cycle is 35 days: 280 days)
Population: Received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Velcade + Fludarabine | Overall Response Rate | 3 participants |
| Rituximab + Fludarabine | Overall Response Rate | 6 participants |