Title A Phase II Trial of Response-Adapted Chemotherapy Based on Positron Emission Tomography for Non-Bulky Stage I and II Hodgkin Lymphoma
IRB CALGB 50604
Hospital Main Campus
Stage Stage 1, Stage 2
Phase Phase 2
Disease Lymphoma, Lymphoma, Hodgkin
- Primary Objective
- To determine the progression-free survival (PFS) from enrollment for patients with non-bulky stage I and II Hodgkin lymphoma. All patients will begin treatment with ABVD. The chemotherapy regimen (ABVD or escalated BEACOPP) and the possible addition of IFRT will be determined by response as assessed by PET imaging after two cycles. The primary endpoint will be the PFS for patients that are PET negative following 2 cycles of ABVD for whom treatment will consist of 2 additional cycles of ABVD without RT. The second primary objective, will be to compare the PFS of patients who are PET positive versus PET negative following 2 cycles of ABVD. Patients who are PET positive after the initial 2 cycles of ABVD will receive 2 cycles of escalated BEACOPP and IFRT.
- Secondary Objectives
- To evaluate the complete response (CR) rate of patients diagnosed with non-bulky stage I and II Hodgkin lymphoma following PET response-adapted chemotherapy with or without radiation therapy.
- To determine the predictive value of FDG uptake using various semiquantitative approaches, at baseline, after 2 cycles of AVBD and at completion of therapy.
- To determine the predictive value of volumetric changes on CT vs 2-D analyses after 2 cycles and 4 cycles and compare with PET parameters with and without combination analyses (PET+dedicated CT data).
- To compare the predictive value of metabolic parameters/changes that are measured both visually and semi-quantitatively, IHP criteria, 2-D and volumetric CT changes, molecular parameters, and conventional parameters, including IPS.
- To assess whether elevated baseline serum soluble CD30 (sCD30), IL10, CCL17, and CCL22 correlate with clinical response and PFS.
- To assess whether persistent or recurrent elevated serial serum sCD30, IL10, CCL17, or CCL22 correlate with relapse/progression or PET scan results.
- To confirm independently useful tissue biomarkers for risk stratification in patients with non-bulky stage I and II Hodgkin lymphoma treated with this regimen.
- To compare mediastinal bulk on standing PA and lateral chest x-ray (>0.33 maximum chest diameter) with chest CT (mass > 10 cm).
- Documentation of Disease
- Histologically documented Hodgkin lymphoma subclassified according to the WHO modification of the Rye Classification and staged according to the modified Ann Arbor Staging Classification system. Patients must have clinical stage IA, IB, IIA or IIB. Patients with "E" extensions will be eligible if all other criteria have been met. Nodular lymphocyte predominant Hodgkin lymphoma is excluded. Core needle biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping. 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. If the original diagnostic specimen is not available, specimens obtained at relapse may be submitted. If multiple specimens are available, please submit the most recent. Failure to submit pathology materials within 60 days of patient registration will be considered a major protocol violation (see Section 5.3).
- Patients may not have a mediastinal mass > 0.33 maximum intrathoracic diameter on standing posteroanterior chest x-ray, or peripheral or retroperitoneal adenopathy > 10 cm in its largest diameter.
- Patient may have had one cycle only of ABVD prior to enrolling on study. No other prior treatment (chemotherapy or radiation therapy) for Hodgkin lymphoma is allowed. If patient has had one cycle of ABVD, in order to be eligible to enroll on CALGB 50604, the patient must have had all of the following tests prior to starting the first cycle of ABVD:
- Chest X-ray, PA and Lateral
- LVEF by ECHO or MUGA
- PFTs (including DLCO/FVC)
- CT scan (neck (SEE NOTE BELOW), chest, abdomen, pelvis)
- FDG-PET/CT scan
- CBC, differential, platelets
- Serum creatinine
- Alkaline phosphatase
- NOTE: Patients with a negative FDG-PET/CT scan do not need to have had a dedicated neck CT scan prior to starting the previous cycle of ABVD.
- Measurable disease must be present either on physical examination or imaging studies. Any tumor mass measurable in two dimensions and > 1 cm is acceptable (or 1.5 cm if 0.5 cm slices are used, as in spiral CT scans). Lesions that are considered intrinsically non-measurable include the following:
- bone lesions
- leptomeningeal disease
- pleural/pericardial effusion
- lymphangitis cutis/pulmonis
- abdominal masses that are not confirmed and followed by imaging techniques
- cystic lesions
- lesions that are situated in a previously irradiated area
- No "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse.
- ECOG performance status 0-2.
- LVEF by ECHO or MUGA within institutional normal limits.
- DLCO ≥ 60% with no symptomatic pulmonary disease.
- HIV positive patients are eligible if they have CD4 counts ≥ 350/mcL. Patient HIV status must be known prior to registration. Patients with a history of intravenous drug abuse or any behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. An HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk. HIV positive patients must not have multi-drug resistant HIV infections; CD4 counts < 350/mcL or other concurrent AIDS-defining conditions.
- Non-pregnant and non-nursing. Due to the teratogenic potential of the agents used in this study, pregnant or nursing women may not be enrolled. Women and men of reproductive potential should agree to use an effective means of birth control.
- Age 18 - 60 years.
- Initial Required Laboratory Values:
- ANC ≥ 1000/µL
- Platelet Count ≥ 100,000/µL
- Serum Creatinine ≤ 2 mg/dL
- Bilirubin ≤ 2 mg/dL
- AST ≤ 2 x upper limit of normal