Non-Hodgkin's Lymphoma
Conditions
Keywords
Follicular non-Hodgkin's lymphoma relapse refractory
Brief summary
Assess the combination of efficacy of the combination of rituximab, bendamustine, mitoxantrone, dexamethasone in the treatment of patients with Follicular Lymphoma.
Detailed description
Assess the combination of efficacy and safety of the combination of rituximab, bendamustine, mitoxantrone, dexamethasone in the treatment of patients with Follicular Lymphoma who are refractory or in relapse.
Interventions
DRUGRituximab, Bendamustine, Mitoxantrone, Dexamethasone
Bendamustine: 90 mg/m2/day, days 1 and 2 of each cycle, iv Mitoxantrone: 6 mg/m2/day, day 1 of each cycle, iv Dexamethasone 20 mg / day, days 1 through 5 of each cycle, od Rituximab: 375 mg / m 2 / day, day 1 of each cycle, iv
Sponsors
Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 and ≤ 75 years. 2. Patients with follicular lymphoma grade 1, 2 or 3a, CD20 +, histologically confirmed lymph node biopsy or tissue. Be accepted diagnosis in bone marrow if no accessible lymph nodes and whether it has discarded the mantle LLC, and NHL. 3. Follicular lymphoma patients treated with the combination of rituximab and chemotherapy in first line, which have been refractory or relapsed after having achieved any responses to this first line of pretreatment (excluding radiotherapy). 4. ECOG ≤ 2. 5. Signed written informed consent.
Exclusion criteria
1. Clinical suspicion or documentation of histological transformation. 2. Have received prior chemotherapy scheme, first line without Rituximab. 3. Prior autologous or allogeneic. 4. CNS infiltration by LF (primary CNS lymphoma or lymphomatous meningitis). 5. Past or active Hepatitis B (at least one of the following markers HBsAg, HBe Ag, anti-HBc, HBV DNA) 6. HCV infection. HIV infection or other conditions of serious immunosuppression. 7. Previous neoplasms except non-melanoma skin cancer of the cervix or adequately treated. 8. Cardiac function in cardiac patient known or prior treatment with anthracyclines with EF \<50%. 9. Impaired renal function (creatinine\> 1.5 x Upper Limit of Normal, LSN) or a creatinine clearance \<50 ml / h, not related to lymphoma. 10. Impaired liver function (bilirubin, AST / ALT or GGT\> 2 x ULN) were not related to lymphoma. 11. Women who are nursing or pregnant. Women of childbearing potential will be included prior pregnancy test serum / urine negative. Use effective contraception to be kept for 1 year after cessation of rituximab. 12. Patients with heart disease, pulmonary, neurological, psychiatric or severe metabolic and not secondary to lymphoma. 13. Severe acute or chronic infection in activity. 14. Any other concurrent medical or psychological comorbidity that might interfere with participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 7 years | The primary endpoint is the number of Participants with Response according to the criteria of the International Workshop to Standardize Response Criteria for NHL Complete Remission (CR): Nodes returned to normal (if GTD \>15 mm before therapy, GTD now ≤15 mm; if GTD 11-15 and SA \>10 mm before therapy, SA now ≤10 mm) All (non-nodal) target lesions completely resolved Partial Remission (PR) SPD of target lesions decreased ≥50% from baseline Spleen and liver nodules regress by 50% in SPD or single lesion in GTD Stable Disease (SD) Not enough shrinkage for PR Not enough growth for PD Progressive Disease (PD): SPD increase ≥50% from nadir (smallest value seen during trial) in nodal target lesions overall or in any single nodal target lesion |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints Included an Assessment of the Following Parameters: Progression-Free Survival, Disease-Free Survival, Global Survival, Duration of the Response. | 7 years |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab, Bendamustine, Mitoxantrone, Dexamethasone Patient will receive Rituximab, Bendamustina, Mitoxantrone and Dexametasona
Rituximab, Bendamustine, Mitoxantrone, Dexamethasone: Bendamustine: 90 mg/m2/day, days 1 and 2 of each cycle, iv Mitoxantrone: 6 mg/m2/day, day 1 of each cycle, iv DEXAMETHASONE 20 mg / day, days 1 through 5 of each cycle, od Rituximab: 375 mg / m 2 / day, day 1 of each cycle, iv | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | Rituximab, Bendamustine, Mitoxantrone, Dexamethasone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 28 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants |
| Age, Continuous | 62 years |
| Region of Enrollment Spain | 60 participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 60 |
| other Total, other adverse events | 60 / 60 |
| serious Total, serious adverse events | 22 / 60 |
Outcome results
Primary
Response Rate
The primary endpoint is the number of Participants with Response according to the criteria of the International Workshop to Standardize Response Criteria for NHL Complete Remission (CR): Nodes returned to normal (if GTD \>15 mm before therapy, GTD now ≤15 mm; if GTD 11-15 and SA \>10 mm before therapy, SA now ≤10 mm) All (non-nodal) target lesions completely resolved Partial Remission (PR) SPD of target lesions decreased ≥50% from baseline Spleen and liver nodules regress by 50% in SPD or single lesion in GTD Stable Disease (SD) Not enough shrinkage for PR Not enough growth for PD Progressive Disease (PD): SPD increase ≥50% from nadir (smallest value seen during trial) in nodal target lesions overall or in any single nodal target lesion
Time frame: 7 years
Population: Number of Participants analyzed in the Maintenance Rituximab Arm reflects all participants who received at least one dose of Rituximab during maintenance, and had available data for response during that phase
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Induction Rituximab, Bendamustine, Mitoxantrone, Dexamethasone | Response Rate | 57 Participants |
| Maintenance Rituximab | Response Rate | 35 Participants |
Secondary
Secondary Endpoints Included an Assessment of the Following Parameters: Progression-Free Survival, Disease-Free Survival, Global Survival, Duration of the Response.
Time frame: 7 years
Population: Only those patients who started the maintenance treatmet were analyzed for Disease-Free Survival
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Induction Rituximab, Bendamustine, Mitoxantrone, Dexamethasone | Secondary Endpoints Included an Assessment of the Following Parameters: Progression-Free Survival, Disease-Free Survival, Global Survival, Duration of the Response. | Progression-Free Survival | 56 months |
| Induction Rituximab, Bendamustine, Mitoxantrone, Dexamethasone | Secondary Endpoints Included an Assessment of the Following Parameters: Progression-Free Survival, Disease-Free Survival, Global Survival, Duration of the Response. | Disease-Free Survival | 51 months |
| Induction Rituximab, Bendamustine, Mitoxantrone, Dexamethasone | Secondary Endpoints Included an Assessment of the Following Parameters: Progression-Free Survival, Disease-Free Survival, Global Survival, Duration of the Response. | Global Survival | NA months |
| Induction Rituximab, Bendamustine, Mitoxantrone, Dexamethasone | Secondary Endpoints Included an Assessment of the Following Parameters: Progression-Free Survival, Disease-Free Survival, Global Survival, Duration of the Response. | Duration of the Response | 54 months |