Clinical Trials

The James Cancer Center Columbus, OH

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Response-Based Therapy Assessed by PET Scan in Treating Patients with Stage IA-IIB Hodgkin Lymphoma

Protocol: CALGB-50801

Full Title

Phase II Trial of Response-Adapted Therapy Based on Positron Emission Tomography (PET) for Bulky Stage I and Stage II Classical Hodgkin Lymphoma

Purpose

This phase II clinical trial studies how well response-based therapy assessed by positron emission tomography (PET) scan works in treating patients with stage IA-IIB Hodgkin lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Radiation therapy uses high energy x-rays to kill cancer cells. Giving chemotherapy together with radiation therapy may kill more cancer cells. Diagnostic procedures, such as PET scan, done before, during, and after chemotherapy may help doctors plan the best treatment.

Study Objective

PRIMARY OBJECTIVES:

I. To determine the progression-free survival (PFS) at 36 months from enrollment for patients with bulky stage I and II Hodgkin lymphoma.

SECONDARY OBJECTIVES:

I. To evaluate the complete response (CR) rate of patients diagnosed with bulky stage I and II Hodgkin lymphoma following positron emission tomography (PET)-response-adapted chemotherapy with or without radiation therapy.

II. To determine the predictive value of fludeoxyglucose (FDG) uptake using various semiquantitative approaches at baseline, after 2 courses of doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine (ABVD), and at completion of therapy.

III. To determine the predictive value of volumetric versus (vs.) 2-dimensional (2-D) measurement changes on computed tomography (CT) between baseline and after 2 cycles, at the end of chemotherapy (PET negative patients only), and after radiotherapy (RT) (PET positive patients only) and compare with PET parameters.

IV. To determine if changes in both qualitative and semiquantitative FDG-PET findings between baseline and after cycle 2, at end of chemotherapy (PET negative patients only) and after RT (PET positive patients only) with combination analyses with incorporating changes obtained from dedicated CT scans, correlate with response and PFS.

V. To compare the predictive value of both qualitative and semiquantitative FDG-PET changes, 2-D and volumetric CT changes, and combinatorial analyses (PET + dedicated CT data) with molecular parameters and conventional parameters, including International Prognostic Score (IPS).

VI. To assess whether elevated baseline serum soluble CD30 (sCD30), interleukin (IL)10, CCL17, and CCL22 correlate with clinical response and PFS.

VII. To assess whether persistent or recurrent elevation of serial serum sCD30, IL10, CCL17, or CCL22 correlate with relapse/progression or PET scan results.

VIII. To confirm independently useful tissue biomarkers (B-cell lymphoma 2 [bcl-2], MAL, FOXP3, CD68, granzyme B [GzB]) for risk stratification in patients with bulky stage I and II Hodgkin lymphoma treated with this regimen.

IX. To compare mediastinal bulk on standing PA and lateral chest x-ray (> 0.33 maximum chest diameter) with chest CT (mass > 10 cm).

OUTLINE:

ABVD CHEMOTHERAPY: All patients receive doxorubicin hydrochloride intravenously (IV) over 3-5 minutes, bleomycin sulfate IV, vinblastine IV over 3-5 minutes, and dacarbazine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo a PET/CT scan and CT scan of the neck (if it was positive at baseline), chest, abdomen, and pelvis. Patients who are PET-positive proceed to escalated bleomycin sulfate, etoposide, doxorubicin hydrochloride, cyclophosphamide, vincristine sulfate, procarbazine hydrochloride and prednisone (BEACOPP) chemotherapy. Patients who are PET-negative receive 4 additional courses of ABVD chemotherapy in the absence of disease progression or unacceptable toxicity.

ESCALATED BEACOPP CHEMOTHERAPY: Patients receive doxorubicin hydrochloride IV over 3-5 minutes and cyclophosphamide IV over 60 minutes on day 1; etoposide IV over 60 minutes on days 1, 2, and 3; procarbazine hydrochloride orally (PO) once daily (QD) on days 1-7; prednisone PO on days 1-14; and bleomycin sulfate IV and vincristine sulfate IV on day 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo another PET/CT scan and CT scan of the neck (if it was positive at baseline), chest, abdomen, and pelvis. Patients then undergo involved-field radiation therapy 5 days per week for 3.5 weeks (for a total of 30.6 Gy).

Within 3-8 weeks after completion of chemotherapy, patients undergo an additional PET/CT scan (utilizing fludeoxyglucose F 18) and CT scan of the neck (if it was positive at baseline), chest, abdomen, and pelvis. Patients who are PET-negative proceed to follow up. Patients who are PET-positive undergo a biopsy*, patients with a negative biopsy proceed to follow up, and patients with a positive biopsy are treated at the discretion of the investigator.

NOTE: *Patients for whom a biopsy is neither clinically appropriate nor medically feasible proceed to follow up. Patients who defer the biopsy undergo scanning 3 months later and then undergo biopsy as above.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually for 7 years.

Are you eligible?

Inclusion Criteria:

Histologically documented Hodgkin lymphoma subclassified according to the World Health Organization (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

Patients must have a mediastinal mass > 0.33 maximum intrathoracic diameter on standing postero-anterior chest x-ray or mass measuring > 10 cm in its largest diameter

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

Patients 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 Cancer and Leukemia Group B (CALGB) 50801, the patient must have had all of the following tests prior to starting the first cycle of ABVD:

Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multi gated acquisition (MUGA)

Pulmonary function tests (PFTs) (including diffusing capacity of the lung for carbon monoxide [DLCO]/forced vital capacity [FVC])

CT scan (neck**, chest, abdomen, pelvis)

FDG-PET/CT scan

Chest X-ray, posterioranterior (PA) & lateral

Complete blood count (CBC), differential, platelets

Erythrocyte sedimentation rate (ESR)

Serum creatinine

Glucose

Aspartate aminotransferase (AST)

Alkaline phosphatase

Bilirubin

Lactate dehydrogenase (LDH)

  • 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

Eastern Cooperative Oncology Group (ECOG) performance status 0-2

LVEF by ECHO or MUGA within institutional normal limits unless thought to be disease related; DLCO >= 60% with no symptomatic pulmonary disease unless thought to be disease related

Patients with known human immunodeficiency virus (HIV) must have a CD4 count > 350 and be on concurrent antiretrovirals; 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

Non-pregnant and non-nursing; women and men of reproductive potential should agree to use an effective means of birth control

Absolute neutrophil count (ANC) >= 1000/uL

Platelet count >= 100,000/uL

Serum creatinine =< 2 mg/dL

Bilirubin* =< 2 x upper limit of normal

In the absence of Gilbert’s disease

AST =< 2 x upper limit of normal

Lymphoma Hodgkin’s Lymphoma