PET-Directed Therapy in Treating Patients With Limited-Stage Diffuse Large B-Cell Lymphoma
Trial Purpose and Description
To assess the 5-year progression-free survival (PFS) rate 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
1) To evaluate progression-free survival within the PET+ and PET- subgroups of patients with newly diagnosed limited stage diffuse large B-cell lymphoma (DLBCL).
2) To evaluate toxicity of the protocol treatments in this patient population.
3) To evaluate the response probability in this patient population.
4) To evaluate overall survival in the overall population, and within the PET+ and PETsubgroups.
5) To estimate the rate of upstaging at baseline by PET/CT among patients newly diagnosed with limited stage diffuse large B-cell lymphoma by CT imaging and describe outcomes in patients upstaged by PET/CT at baseline to advanced DLBCL.
6) To describe outcomes in the subgroup of patients upstaged by PET/CT.7) 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 (OS).
- 18 Years and older
INITIAL REGISTRATION (STEP 1)
Patients must have biopsy-proven Diffuse Large B-cell Lymphoma. Patients with primary mediastinal lymphoma or testicular lymphoma are not eligible.
Patients must have non-bulky Stage I or II disease by Ann Arbor classification. This staging excludes FDG-PET evaluation. Patients who have Stage I or II non-bulky disease based on diagnostic CT scan, but are upstaged to Stage III or IV based on FDG-PET evaluation are also eligible. Stage and bulk are assigned using measurements obtained prior to biopsy.
Patients must have a diagnostic quality contrast-enhanced CT scan of the chest, abdomen and pelvis AND baseline FDG-PET scan performed within 28 days prior to registration. Low resolution "localization" CT scans performed as part of a combined PET/CT scan are not adequate for enrollment or response determination on this protocol. If the patient has an allergy to CT contrast, then a non-enhanced CT will be acceptable.
Patients must not have clinical evidence of central nervous system involvement by lymphoma, since proposed treatment would not be able to address it adequately. Any laboratory or radiographic tests performed to assess CNS involvement must be negative and must be performed within 42 days prior to registration.
Patients may have either measurable or evaluable limited-stage DLBCL. Patients rendered free of measurable or evaluable disease by virtue of biopsy (resection) are also eligible. NOTE: If patient has measurable disease it must be documented on the Lymphoma Baseline Tumor Assessment Form. All measurable disease must be assessed within 28 days prior to registration. Patients with non-measurable disease with or without measurable disease must have all non-measurable disease assessed within 42 days prior to registration.
Patients must have a unilateral or bilateral bone marrow biopsy performed within 42 days prior to registration. Pathology Review: Adequate sections or a paraffin block from the original diagnostic specimen must be submitted for review by the lymphoma pathology group.
Patients must be offered the opportunity to consent to the use of specimens for future research.
The lymphoma must express the CD20 antigen by either flow cytometry using anti-CD20 antibodies or by immunoperoxidase staining of paraffin sections. A report providing confirmation of CD20 expression must be submitted.
Patients must have passed their 18th birthday.
Patients must not have received prior chemotherapy, radiation, or antibody therapy for lymphoma.
Patients must have a Zubrod performance status of 0 - 2.
The following tests must be performed within 42 days prior to registration either for diagnosis/staging or to obtain baseline values:
d. Serum creatinine
Patients must have platelet count ≥ 100,000 cells/mcL and ANC ≥ 1,000 cells/mcL within 42 days prior to registration 5.16 Patients must have total bilirubin ≤ 2 x Institutional Upper Limit of Normal (IULN) (unless due to Gilbert’s Syndrome) within 42 days prior to registration.
Patients must not be known to be HIV-positive due to poor specificity of PET/CT scans in this population.
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years.
Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. Women/men of reproductive potential must have agreed to use an effective contraceptive method during the study period. A woman is considered to be "of reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive meaures.
All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.
SECOND REGISTRATION (STEP 2)
Patients must have completed 3 cycles of R-CHOP with no evidence of disease progression.
Interim PET/CT scans must have been submitted for centralized review. If PET-negative based on the returned results from centralized review, patients must be planning to begin further treatment within 35 days of the start of Cycle 3 of R-CHOP. If PET-positive based on the returned results from centralized review, it is important for patients to start IFRT as soon as possible after the end of Cycle 3 of R-CHOP. They should be planning to initiate IFRT followed by yttrium-90 ibritumomab tiuxetan within 35 days of the start of Cycle 3 of RCHOP.
- Southwestern Oncology Group (SWOG)
- September 2012
- Last Updated:
- Study HIC#:
Clinicaltrials.gov ID: Yale3293682