Follicular Lymphoma
Conditions
Brief summary
This is a phase 2, single-arm, open label, multicenter study evaluating the efficacy and safety of the combination of VELCADE, bendamustine, and rituximab in subjects with relapsed or refractory follicular lymphoma, who have received 4 or more doses of rituximab. Subjects may be sensitive or refractory to prior therapies, including rituximab.
Interventions
DRUGVELCADE
VELCADE administered as a 3- to 5-second intravenous (IV) bolus prior to Bendamustine and Rituximab on Days 1,8,15 and 22 of each cycle.
DRUGBendamustine
Bendamustine administered IV over 30-60 minutes after VELCADE on Days 1 and 2 of each cycle
DRUGRituximab
Rituximab administered by IV infusion after VELCADE and Bendamustine on Days 1, 8, 15 and 22 of Cycle 1, and on Day 1 of Cycles 2, 3, 4 and 5
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subject 18 years of age or older * Pathological diagnosis of follicular lymphoma (any grade) * Documented relapse or progression following prior antineoplastic therapy * Have received 4 or more prior doses of rituximab * At least 1 measurable tumor mass (\>1.5 cm in the long axis and \>1.0 cm in the short axis that has not been previously irradiated, or has grown since previous irradiation * No clinically significant central nervous system lymphoma * Karnofsky performance status (KPS) ≥50 (equivalent to Eastern Cooperative Group Oncology Group \[ECOG\] status ≤2
Exclusion criteria
* Diagnosed or treated for a malignancy other than non-Hodgkin's lymphoma (NHL) within 2 years of first dose, or who were previously diagnosed with a malignancy other than NHL and have any radiographic or biochemical marker evidence of malignancy. Subjects with prostate cancer who were treated with definitive radiotherapy and have a serum prostate-specific antigen (PSA) \<1 ng/mL are not excluded. Subjects are also not excluded if they have had basal cell or squamous cell carcinoma of the skin that was completely resected, or any in situ malignancy that was adequately treated. * Prior treatment with VELCADE® or bendamustine * Antineoplastic (including unconjugated therapeutic antibodies and toxin immunoconjugates), experimental, or radiation therapy within 3 weeks before Day 1 of Cycle 1 * Nitrosoureas within 6 weeks before Day 1 of Cycle 1 * Radioimmunoconjugates within 10 weeks before Day 1 of Cycle 1 * Autologous stem cell transplant within 3 months before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time * Major surgery within 2 weeks before Day 1 of Cycle 1 * Platelet transfusion within 7 days of Day 1 of Cycle 1 (applies to subjects enrolled in the dose escalation phase only. This does not apply to subjects enrolled in phase 2 of the study). * Ongoing therapy with corticosteroids. Prednisone ≤15 mg per day or its equivalent is allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Response | 12 weeks after the last subject completes their end of treatment visit. | Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Response (Complete and Partial Response) | 12 weeks after the last subject completes their end of treatment visit | Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease. Partial response requires regression of measurable disease and no new sites. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VELCADE, Bendamustine, Rituximab (VBR) Treatment Patients receive bortezomib 1.6 mg/m\^2 IV on days 1, 8, 15, and 22 of each 35-day cycle; bendamustine 50-90 mg/m\^2 IV on days 1 and 2 of each cycle; rituximab 375 mg/m\^2 IV on days 1, 8, 15 and 22 of cycle 1 and on day1 of cycles 2, 3, 4, and 5. Total treatment duration is 5 cycles. | 73 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 16 |
| Overall Study | Other | 3 |
| Overall Study | Physician Decision | 7 |
| Overall Study | Progressive Disease | 4 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | VELCADE, Bendamustine, Rituximab (VBR) Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 24 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants |
| Age Continuous | 59.8 years STANDARD_DEVIATION 10.36 |
| Region of Enrollment United States | 73 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 72 / 73 |
| serious Total, serious adverse events | 25 / 73 |
Outcome results
Primary
Number of Participants With Complete Response
Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease.
Time frame: 12 weeks after the last subject completes their end of treatment visit.
Population: Response-evaluable population is defined at patients treated with 90 mg/m\^2 bendamustine, received at least one dose of any study drug, and had at least one post baseline response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VELCADE, Bendamustine, Rituximab (VBR) Treatment | Number of Participants With Complete Response | 32 participants |
Secondary
Number of Participants With Overall Response (Complete and Partial Response)
Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease. Partial response requires regression of measurable disease and no new sites.
Time frame: 12 weeks after the last subject completes their end of treatment visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VELCADE, Bendamustine, Rituximab (VBR) Treatment | Number of Participants With Overall Response (Complete and Partial Response) | 53 participants |