Relapsed Follicular Lymphoma
Conditions
Brief summary
This is a phase 2, two-arm, non-randomized, open-label, multicenter study evaluating the safety and efficacy of 2 VELCADE-containing regimens. Patients will be treated with either a combination of VELCADE, rituximab, cyclophosphamide, doxorubicin, and prednisone (VELCADE-R-CAP) or a combination of VELCADE, rituximab, cyclophosphamide, and prednisone (VELCADE-R-CP) based on investigator preference. Following completion of the treatment period, patients will receive maintenance therapy with rituximab up to a maximum of 2 years.
Interventions
DRUGrituximab
DRUGcyclophosphamide
DRUGdoxorubicin
DRUGVELCADE
DRUGprednisone
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
NON_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 patient 18 years of age or older * Pathological diagnosis of follicular lymphoma (any grade) or marginal zone lymphoma. Patients with transformed follicular lymphoma are eligible, provided there has previously been pathologic documentation of follicular lymphoma. * Documented relapse or progression following prior antineoplastic therapy * At least 1 measurable tumor mass that is greater than 1.5 cm in the long axis and greater than 1.0 cm in the short axis that has not been previously irradiated, or has grown since previous irradiation * No clinically significant evidence of active 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. Patients with prostate cancer who were treated with definitive radiotherapy who have a serum prostate-specific antigen \<1 ng/mL are not excluded. Patients are 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. * Received any of the following treatments or procedures outside of the specified timeframes: * Prior treatment with VELCADE * Prior treatment with a cumulative dose of doxorubicin of more than 100 mg/m2, if assigned to Arm A (VELCADE-R-CAP) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Complete Response (CR) | 30 weeks | Disappearance of all evidence of disease assessed by computed tomography (CT) and PET (position-emission tomography) according to the revised International Working Group (IWG) Criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Response (OR) | 30 weeks | OR = Complete Response (CR) + Partial Response (PR)according to the revised International Working Group (IWG) Criteria. CR is the disappearance of all evidence of disease assessed by CT and PET. PR is the regression of measurable disease and no new sites assessed by CT and PET. |
| Percentage of Participants With Progression-free Survival (PFS) at 1 Year | Assessed at at the end of Cycle 2, at end of treatment visit, and every 12± 1 weeks for the first year (4 visits) until PD | PFS was defined as the time from the first dose to the date of progressive disease (PD)/relapse or death, whichever comes first. For a participant who had not progressed/relapsed or died, PFS was censored at the last response assessment that was stable disease (failure to attain complete response/partial response or PD or better). |
| Duration of Response | 2 years | Time (in months) from the first documentation of a response (CR or partial response \[PR\]) to the date of first documentation of progressive disease or relapse from complete response. CR is defined as disappearance of all evidence of disease assessed by CT or PET; PR is defined as regression of measurable disease and no new sites assessed by CT or PET according to the revised International Working Group (IWG) Criteria. |
| Number of Patients Who Experienced at Least One Serious Adverse Event | From completion of informed consent through 30 days after the last dose of study drug | — |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VELCADE R-CAP VELCADE, rituximab, cyclophosphamide, prednisone, and Doxorubicin | 7 |
| VELCADE R-CP VELCADE, rituximab, cyclophosphamide, and prednisone | 48 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 6 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | VELCADE R-CP | VELCADE R-CAP | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 0 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 7 Participants | 34 Participants |
| Age Continuous | 62.3 years STANDARD_DEVIATION 11.39 | 62.9 years STANDARD_DEVIATION 8.3 | 62.3 years STANDARD_DEVIATION 10.98 |
| Region of Enrollment United States | 48 participants | 7 participants | 55 participants |
| Sex: Female, Male Female | 24 Participants | 5 Participants | 29 Participants |
| Sex: Female, Male Male | 24 Participants | 2 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 47 / 48 |
| serious Total, serious adverse events | 2 / 7 | 12 / 48 |
Outcome results
Primary
Number of Patients With Complete Response (CR)
Disappearance of all evidence of disease assessed by computed tomography (CT) and PET (position-emission tomography) according to the revised International Working Group (IWG) Criteria.
Time frame: 30 weeks
Population: Response evaluable: measurable disease at baseline, completed first scheduled response evaluation, or do not complete first scheduled response evaluation due to progressive disease (PD) or death.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VELCADE R-CAP | Number of Patients With Complete Response (CR) | 1 participants |
| VELCADE R-CP | Number of Patients With Complete Response (CR) | 13 participants |
Secondary
Duration of Response
Time (in months) from the first documentation of a response (CR or partial response \[PR\]) to the date of first documentation of progressive disease or relapse from complete response. CR is defined as disappearance of all evidence of disease assessed by CT or PET; PR is defined as regression of measurable disease and no new sites assessed by CT or PET according to the revised International Working Group (IWG) Criteria.
Time frame: 2 years
Population: Responders: CR + PR (Not done for VELCADE R-CAP, only 5 responders)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| VELCADE R-CP | Duration of Response | 21.9 Months |
Secondary
Number of Participants With Overall Response (OR)
OR = Complete Response (CR) + Partial Response (PR)according to the revised International Working Group (IWG) Criteria. CR is the disappearance of all evidence of disease assessed by CT and PET. PR is the regression of measurable disease and no new sites assessed by CT and PET.
Time frame: 30 weeks
Population: Response evaluable: measurable disease at baseline, completed first scheduled response evaluation, or do not complete first scheduled response evaluation due to PD or death.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VELCADE R-CAP | Number of Participants With Overall Response (OR) | 6 participants |
| VELCADE R-CP | Number of Participants With Overall Response (OR) | 37 participants |
Secondary
Number of Patients Who Experienced at Least One Serious Adverse Event
Time frame: From completion of informed consent through 30 days after the last dose of study drug
Population: Safety Population: Treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VELCADE R-CAP | Number of Patients Who Experienced at Least One Serious Adverse Event | 2 participants |
| VELCADE R-CP | Number of Patients Who Experienced at Least One Serious Adverse Event | 12 participants |
Secondary
Percentage of Participants With Progression-free Survival (PFS) at 1 Year
PFS was defined as the time from the first dose to the date of progressive disease (PD)/relapse or death, whichever comes first. For a participant who had not progressed/relapsed or died, PFS was censored at the last response assessment that was stable disease (failure to attain complete response/partial response or PD or better).
Time frame: Assessed at at the end of Cycle 2, at end of treatment visit, and every 12± 1 weeks for the first year (4 visits) until PD
Population: Safety population: Treated
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VELCADE R-CAP | Percentage of Participants With Progression-free Survival (PFS) at 1 Year | 67 percentage of participants |
| VELCADE R-CP | Percentage of Participants With Progression-free Survival (PFS) at 1 Year | 63 percentage of participants |