S1001 PET-Directed Therapy in Treating Patients With Limited-Stage Diffuse Large B-Cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT01359592|
Recruitment Status : Active, not recruiting
First Posted : May 25, 2011
Last Update Posted : October 5, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate Other: R-CHOP regimen Other: laboratory biomarker analysis Radiation: fludeoxyglucose F 18 Radiation: selective external radiation therapy Radiation: yttrium Y 90 ibritumomab tiuxetan||Phase 2|
- 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).
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||159 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of PET-Directed Therapy for Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL)|
|Study Start Date :||September 2011|
|Estimated Primary Completion Date :||June 2020|
|Estimated Study Completion Date :||March 2024|
Active Comparator: PET Negative: R-CHOP
R-CHOP x 3 Cycles
|Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate Other: R-CHOP regimen Other: laboratory biomarker analysis|
Experimental: PET Positive: IFRT +Zevalin
Standard IFRT+ Zevalin IV per ABW
|Biological: rituximab Other: laboratory biomarker analysis Radiation: fludeoxyglucose F 18 Radiation: selective external radiation therapy Radiation: yttrium Y 90 ibritumomab tiuxetan|
- Five-year PFS rate of patients with DLBCL [ Time Frame: 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.
- PFS within the PET+ and PET- subgroups of patients with newly diagnosed limited-stage DLBCL [ Time Frame: 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.
- Toxicity of protocol treatments [ Time Frame: Up to 4 months ]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 DLBCL [ Time Frame: 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.
- Association of germinal center B-cell subtype (GCB) vs stromal-1 vs stromal-2 gene expression signatures with PFS or overall survival [ Time Frame: 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01359592
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|Principal Investigator:||Daniel O. Persky, MD||Yale University|