S1001 PET-Directed Therapy in Treating Patients With Limited-Stage Diffuse Large B-Cell Lymphoma
- Conditions
- Lymphoma
- Interventions
- Other: laboratory biomarker analysisRadiation: fludeoxyglucose F 18Radiation: selective external radiation therapyRadiation: yttrium Y 90 ibritumomab tiuxetanOther: R-CHOP regimen
- Registration Number
- NCT01359592
- Lead Sponsor
- SWOG Cancer Research Network
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Monoclonal antibodies, such as 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. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Comparing results of diagnostic procedures, such as PET scan and CT scan, done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment.
PURPOSE: This phase II trial studies how well PET-directed chemotherapy works in treating patients with limited-stage diffuse large B-cell lymphoma.
- Detailed Description
OBJECTIVES:
Primary
* To assess the 5-year progression-free survival (PFS) rate in patients with newly diagnosed limited-stage diffuse, large B-cell lymphoma (DLBCL) using positron emission tomography (PET)/CT scan to direct therapy after 3 courses of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP).
Secondary
* To evaluate PFS within the PET-positive (+) and PET-negative (-) subgroups of patients with newly diagnosed limited-stage DLBCL.
* To evaluate toxicity of the protocol treatments in this patient population.
* To evaluate the response probability in this patient population.
* To evaluate overall survival in the overall population, and within the PET+ and PET- subgroups.
* To estimate the rate of upstaging at baseline by PET/CT at baseline among patients newly diagnosed with limited-stage DLBCL by CT imaging and to describe outcomes in patients upstaged by PET/CT at baseline to advanced DLBCL.
* To describe outcomes in the subgroup of patients upstaged by PET/CT.
* To evaluate the association of germinal center B-cell subtype (GCB) vs stromal-1 vs stromal-2 gene expression signatures with PFS or overall survival.
OUTLINE: This is a multicenter study. Patients are stratified according to whether the patient was upstaged to advanced stage DLBCL, based on local review of the baseline PET/CT (yes vs no).
Chemotherapy: Patients receive R-CHOP comprising rituximab IV, cyclophosphamide IV over 30-60 minutes, vincristine sulfate IV, and doxorubicin hydrochloride IV on day 1, and prednisone orally on days 1-5. Treatment repeats every 21 days for 3\* courses. NOTE: \*Patients found to have advanced stage DLBCL based on local review of the baseline PET scan receive 6 courses of R-CHOP.
FDG/PET - Radiotherapy: Patients undergo fludeoxyglucose F 18 positron emission tomography (FDG-PET)/CT scan at baseline, on days 15-18 of course 3, and at 12 weeks after completion of course 3. Patients with complete response (PET scan negative) receive one additional course of R-CHOP as above. Patients with partial response (PET scan positive) undergo involved-field radiotherapy (IFRT) 5 days a week for approximately 4-5 weeks.
Monoclonal antibody: Beginning 3-6 weeks after completion of IFRT, patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes and rituximab IV on day 1 and on day 7, 8, or 9.
Patients may undergo blood sample collection at baseline for correlative studies. Bone marrow tissue samples may be also collected for correlative studies.
After completion of study therapy, patients are followed up every 6 months for 2 years and then yearly for 5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 159
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PET Positive: IFRT +Zevalin laboratory biomarker analysis Standard IFRT+ Zevalin IV per ABW PET Negative: R-CHOP cyclophosphamide R-CHOP x 3 Cycles PET Negative: R-CHOP rituximab R-CHOP x 3 Cycles PET Negative: R-CHOP laboratory biomarker analysis R-CHOP x 3 Cycles PET Positive: IFRT +Zevalin rituximab Standard IFRT+ Zevalin IV per ABW PET Negative: R-CHOP vincristine sulfate R-CHOP x 3 Cycles PET Negative: R-CHOP R-CHOP regimen R-CHOP x 3 Cycles PET Positive: IFRT +Zevalin selective external radiation therapy Standard IFRT+ Zevalin IV per ABW PET Positive: IFRT +Zevalin fludeoxyglucose F 18 Standard IFRT+ Zevalin IV per ABW PET Positive: IFRT +Zevalin yttrium Y 90 ibritumomab tiuxetan Standard IFRT+ Zevalin IV per ABW PET Negative: R-CHOP doxorubicin hydrochloride R-CHOP x 3 Cycles PET Negative: R-CHOP prednisone R-CHOP x 3 Cycles
- Primary Outcome Measures
Name Time Method Five-year Progression-free Survival (PFS) Rate in Patients With Newly Diagnosed Limited Stage Diffuse Large B-cell Lymphoma (DLBCL) up to 5 years Measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive without report of progression or relapse are censored at date of last contact.
Progressions is defined using the 2007 revised Cheson et. Al. criteria, as ≥50% increase in the sum of the products of diameters (SPD) of target measurable lesions, appearance of any new bone marrow involvement, or appearance of any new lesion \>1.5 cm in the longest axis.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) Within the PET+ and PET- Subgroups of Patients With Newly Diagnosed Limited-stage Diffuse Large B-Cell Lymphoma (DLBCL) up to 5 years Measured from date of interim positron emission tomography (PET)/computed tomography scan to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive without report of progression or relapse are censored at date of last contact.
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug up to 4 months or time of disease progression. Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Overall Survival of Patients With Newly Diagnosed Limited-stage Diffuse Large B-Cell Lymphoma (DLBCL) up to 5 years Measured from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Response Rates in Patients With Newly Diagnosed Limited Stage Diffuse Large B-cell Lymphoma Using PET/CT Scan to Direct Therapy After 3 Cycles of R-CHOP Up to 4 months Complete Response (CR) is a complete disappearance of all disease with the exception of the following. If no PET scan or when the PET scan was positive before therapy, a post-treatment residual mass of any size is permitted if it is PET negative. If the PET scan was negative before therapy, all nodal masses at baseline must have regressed. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response (PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. If PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.
Association of Germinal Center B-cell Subtype (GCB) vs Stromal-1 vs Stromal-2 Gene Expression Signatures With PFS or Overall Survival. 5 years Formalin-fixed, paraffin-embedded tissue from the diagnostic biopsy is collected and used to determine germinal center B-cell (GCB) phenotype. GCB subtype of DLBCL is defined by gene-expression profiling that is performed using quantitative nuclease protection assay (qNPA).
Data for this outcome measure is not available at this time. We expect this data to be available by December 2025.
Trial Locations
- Locations (240)
Providence Cancer Center
🇺🇸Anchorage, Alaska, United States
Arizona Cancer Center at University of Arizona Health Sciences Center
🇺🇸Tucson, Arizona, United States
Aurora Presbyterian Hospital
🇺🇸Aurora, Colorado, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Penrose Cancer Center at Penrose Hospital
🇺🇸Colorado Springs, Colorado, United States
St. Anthony Central Hospital
🇺🇸Denver, Colorado, United States
Kaiser Permanente - Denver
🇺🇸Denver, Colorado, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Presbyterian - St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
St. Joseph Hospital
🇺🇸Denver, Colorado, United States
Scroll for more (230 remaining)Providence Cancer Center🇺🇸Anchorage, Alaska, United States