Lymphoma
Conditions
Keywords
stage II grade 1 follicular lymphoma, stage II grade 2 follicular lymphoma, stage II grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma
Brief summary
RATIONALE: Monoclonal antibodies, such as epratuzumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving epratuzumab and rituximab together may be more effective in treating follicular non-Hodgkin lymphoma. PURPOSE: This phase II trial is studying how well giving epratuzumab together with rituximab works in treating patients with previously untreated follicular non-Hodgkin lymphoma.
Detailed description
OBJECTIVES: Primary * To determine the response rate (overall and complete) after extended induction therapy comprising epratuzumab and rituximab in patients with previously untreated CD20+ follicular non-Hodgkin lymphoma (NHL). * To determine the time to progression after extended induction therapy comprising epratuzumab and rituximab in patients with previously untreated CD20+ follicular NHL. Secondary * To determine the toxicity profile of epratuzumab and rituximab in patients with previously untreated CD20+ follicular NHL. * To establish whether the therapeutic effects of the combination of epratuzumab and rituximab are sufficiently promising to warrant evaluation in a subsequent randomized trial (in comparison to rituximab alone). * To determine the relationship between the change in fludeoxyglucose F 18 uptake early after epratuzumab and rituximab treatment with response rate and time to progression. OUTLINE: * Induction therapy (month 1): Patients receive epratuzumab IV over 5-30 minutes on days 1, 8, 15, and 22 and rituximab IV on days 3, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity. * Extended induction therapy (months 3, 5, 7, and 9): Patients receive epratuzumab IV over 5-30 minutes followed by rituximab IV in weeks 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity. Patients receive fludeoxyglucose F 18 (FDG) subcutaneously and undergo positron emission tomography at baseline and after induction therapy to assess the degree of FDG uptake. After completion of study treatment, patients are followed every 4 months for 2 years then every 6 months for up to 10 years.
Interventions
BIOLOGICALepratuzumab
Days 1, 8, 15, 22 and weeks 12, 20, 28, & 36: 360mg/sq m IV
BIOLOGICALrituximab
Day 3, 8, 15, 22 and weeks 12, 20, 28, & 36: 375mg/sq m IV
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
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
DISEASE CHARACTERISTICS: * Histologically\* confirmed follicular non-Hodgkin lymphoma (NHL) * Previously untreated disease * WHO classification grade 1, 2, or 3a (\> 15 centroblasts per high power field with centrocytes present) that is stage III, IV, or bulky (i.e., single mass ≥ 7 cm in any unidimensional measurement) stage II disease NOTE: \*Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine-needle aspirates are not acceptable for diagnosis * Confirmed CD20 antigen expression by flow cytometry or immunohistochemistry * Measurable disease by physical examination or imaging studies * Any tumor mass \> 1 cm is acceptable * No nonmeasurable disease only, including any of the following: * Bone lesions * Ascites * Pleural/pericardial effusion * Lymphangitis cutis/pulmonis * Bone marrow (involvement by NHL should be noted) * No known CNS involvement by lymphoma * Required to participate in companion FDG-PET imaging study CALGB 580701 PATIENT CHARACTERISTICS: * ECOG performance status ≤ 2 * Absolute neutrophil count ≥ 1,000/μL * Platelet count ≥ 50,000/μL * Patients with HIV infection are eligible provided they meet the following criteria: * No evidence of coinfection with hepatitis B or C * CD4+ cell count ≥ 400/mm\^3 * No evidence of resistant strains of HIV * If not on anti-HIV therapy, HIV viral load \< 10,000 copies HIV RNA/mL * If on anti-HIV therapy, HIV viral load \< 50 copies HIV RNA/mL * No history of AIDS-defining conditions * Not pregnant or nursing * Fertile patients must use effective contraception during and for 3 months after completion of study therapy * No known Human Anti-Chimeric Antibody (HACA)-positivity PRIOR CONCURRENT THERAPY: * No prior therapy for NHL including chemotherapy, radiotherapy, or immunotherapy (e.g., monoclonal antibody-based therapy) * More than 2 weeks since prior corticosteroids except for maintenance therapy for non-malignant disease * No concurrent dexamethasone or other steroids as antiemetics except for the following circumstances: * Treatment of acute infusion reactions according to institutional procedures * No concurrent hormonal therapy except steroids for adrenal failure OR hormones for non-disease-related conditions (e.g., insulin for diabetes) * No other concurrent chemotherapeutic agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Response | 12 months | Overall response is defined as achievement of a complete response (CR) or partial response (PR) as defined by the Revised Response Criteria for Malignant Lymphoma. CR: complete disappearance of all detectable disease PR: \>=50% decrease in the sum of the product of diameters of indicator lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Duration of study (up to 10 years) | Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method. |
Countries
United States
Participant flow
Recruitment details
Between March 2008 and July 2009, 60 participants were recruited.
Pre-assignment details
One participant was deemed ineligible and excluded from all analyses per study design.
Participants by arm
| Arm | Count |
|---|---|
| Epratuzumab Plus Rituximab Induction Therapy (Month 1):
Epratuzumab 360 mg/m\^2 by IV days 1, 8, 15 & 22; Rituximab 375 mg/m\^2 by IV day 3, 8, 15 & 22
Extended Induction (Weeks 12, 20, 28 & 36) Epratuzumab 360 mg/m\^2 by IV weeks 12, 20, 28 & 36; Rituximab 375 mg/m\^2 by IV weeks 12, 20, 28 & 36 | 59 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 1 |
| Overall Study | Progression | 1 |
Baseline characteristics
| Characteristic | Epratuzumab Plus Rituximab |
|---|---|
| Age, Continuous | 54 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 54 Participants |
| Region of Enrollment United States | 59 participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 58 / 59 |
| serious Total, serious adverse events | 10 / 59 |
Outcome results
Primary
Number of Participants With Overall Response
Overall response is defined as achievement of a complete response (CR) or partial response (PR) as defined by the Revised Response Criteria for Malignant Lymphoma. CR: complete disappearance of all detectable disease PR: \>=50% decrease in the sum of the product of diameters of indicator lesions
Time frame: 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Epratuzumab Plus Rituximab | Number of Participants With Overall Response | Complete Response | 25 participants |
| Epratuzumab Plus Rituximab | Number of Participants With Overall Response | Partial Response | 27 participants |
Secondary
Progression Free Survival
Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.
Time frame: Duration of study (up to 10 years)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epratuzumab Plus Rituximab | Progression Free Survival | 3.5 years |
Post Hoc
3-Year Overall Survival
Percentage of participants who were alive at 3 years. The 3 year survival, with 95% confidence interval, was estimated using the Kaplan Meier method.
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epratuzumab Plus Rituximab | 3-Year Overall Survival | 91 percentage of participants |