ECOG 1496 Trial
Proven dosing strategy for helping NHL patients extend remission
ECOG 1496 TRIAL DESIGN1
- *CVP=cyclophosphamide 1 g/m2 on Day 1; vincristine 1.4 mg/m2 on Day 1; prednisone 100 mg/m2 on Days 1–5. After the completion of 6 to 8 twenty-one–day cycles of CVP, patients achieving a CR, PR, or SD were randomized to receive no further treatment or to receive post-induction therapy with RITUXAN. Beginning 4 weeks after completion of induction therapy, patients randomized to RITUXAN received 1 cycle of 4 weekly treatments with 375 mg/m2 RITUXAN, every 6 months for up to 4 cycles.1
- ECOG=Eastern Cooperative Oncology Group; NHL=non-Hodgkin's lymphoma; IWF=International Working Formulation; CR=complete response; PR=partial response; SD=stable disease; PFS=progression-free survival.
ECOG 1496 dosing strategy based on proven B-cell depletion and recovery
B-CELL DEPLETION AFTER RITUXAN MONOTHERAPY IN THE McLAUGHLIN TRIAL2
- McLaughlin P et al. J Clin Oncol. 1998;16:2825-2833.
- In the McLaughlin monotherapy trial in relapsed or refractory, low-grade or follicular NHL2:
- RITUXAN 375 mg/m2 was administered once weekly for 4 weeks
- B cells were rapidly depleted after 4 doses of RITUXAN
- Recovery began at 6 months and returned to baseline levels by 12 months after completion of a 4-week course of RITUXAN monotherapy
- B-cell depletion observed in the McLaughlin trial formed the basis for the ECOG 1496 dosing strategy following first-line CVP induction in low-grade NHL2
The ECOG 1496 trial included both low- and high-risk patients
|Age range (years)||26-84||26-85|
|Elevated LDH (>1×ULN)||24%||21%|
|Ann Arbor Stage||I/II III/IV||
|ECOG performance status||01||
|Bulky disease (>10cm)||19%||24%|
|Number of extranodal sites||01≥2||
|CRF-derived IPI score†||0-1 2 3-4||
- †The IPI score, which ranged from 0 to 5, was derived by assigning 1 point for each of the following risk factors: >60 years of age, Ann Arbor Stage III or IV, extranodal disease involvement at >1 site, ECOG performance status ≥2, and elevated LDH.
- R=RITUXAN; Obs=observation; LDH=lactate dehydrogenase; ULN=upper limit of normal; CRF=case report form; IPI=International Prognostic Index.
- The ECOG 1496 trial's diverse patient population included3:
- Patients across a broad spectrum of age groups (range: 26 to 85 years of age)
- Higher-risk patients with elevated LDH levels and bulky disease
- Lower-risk patients with ECOG performance status of 0-1
RITUXAN after first-line CVP induction more than doubled the likelihood of remaining progression-free at 2.3-year follow-up
- Patients with advanced low-grade NHL were randomized to receive either RITUXAN or no further therapy if they achieved a CR, PR, or SD with CVP induction therapy3
- At 2.3 year median follow-up, there was a 51% reduction in the risk of relapse, progression, or death with RITUXAN vs observation (p≤0.05)3,4
Single-agent RITUXAN for low-grade NHL after first-line CVP chemotherapy
- Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more frequently (≥2%) in the RITUXAN arm compared with those who received no further therapy (4% vs. 1%)
- The following common adverse reactions were reported more frequently (≥5%) in patients receiving RITUXAN following CVP compared with those who received no further therapy: fatigue (39% vs. 14%), anemia (35% vs. 20%), peripheral sensory neuropathy (30% vs. 18%), infections (19% vs. 9%), pulmonary toxicity (18% vs. 10%), hepatobiliary toxicity (17% vs. 7%), rash and/or pruritus (17% vs. 5%), arthralgia (12% vs. 3%), and weight gain (11% vs. 4%)
- Hochster H, Weller E, Gascoyne RD, et al. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG 1496 study. J Clin Oncol. 2009;27:1607-1614.
- McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825-2833.
- Data on file, Genentech, Inc.
- RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2013.