Chemotherapy Based on Positron Emission Tomography Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma

Study Overview
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Brief Summary
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This phase II trial studies how well chemotherapy based on positron emission tomography (PET) scan works in treating patients with stage I or stage II Hodgkin lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Radiation therapy uses high energy x-rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells and allow doctors to save the part of the body where the cancer started. Comparing results of diagnostic procedures, such as PET scan, done before, during, and after chemotherapy may help doctors predict a patient's response to treatment and help plan the best treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the progression-free survival (PFS) from enrollment for patients with non-bulky stage I and II Hodgkin lymphoma. II. To compare the PFS of patients who are PET positive versus PET negative following 2 cycles of doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD). SECONDARY OBJECTIVES: I. 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. II. To determine the predictive value of fludeoxyglucose (FDG) uptake using various semi-quantitative approaches, at baseline, after 2 cycles of AVBD and at completion of therapy. III. To determine the predictive value of volumetric changes on computed tomography (CT) vs 2-dimensional (2-D) analyses after 2 cycles and 4 cycles and compare with PET parameters with and without combination analyses (PET + dedicated CT data). IV. To compare the predictive value of metabolic parameters/changes that are measured both visually and semi-quantitatively, International Harmonization Project (IHP) criteria, 2-D and volumetric CT changes, molecular parameters, and conventional parameters, including International Prognostic Score (IPS). V. To assess whether elevated baseline circulating markers of inflammation (including soluble cluster of differentiation CD30 [sCD]30, soluble CD 163 [CD163], interleukin-10 (IL10), chemokine (C-C motif) ligand 17 (CCL17), and chemokine (C-C motif) ligand 22 [CCL22]) correlate with clinical response and PFS and PET scan results. VI. To assess whether persistent or recurrent elevated serial circulating markers of inflammation (including soluble CD30 [sCD30], soluble CD163 [sCD163], IL10, CCL17, or CCL22) correlate with relapse/progression or PET scan results. VII. To confirm independently useful tissue biomarkers for risk stratification in patients with non-bulky stage I and II Hodgkin lymphoma treated with this regimen. VIII. To compare mediastinal bulk on standing posterior-anterior (PA) and lateral chest x-ray (> 0.33 maximum chest diameter) with chest CT (mass > 10 cm). OUTLINE: ABVD CHEMOTHERAPY: Patients receive doxorubicin hydrochloride intravenously (IV) over 3-5 minutes, bleomycin sulfate IV over 3-5 minutes, 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. Patients then undergo PET scan. Patients achieving complete response (CR), partial response (PR), or stable disease (SD) with a negative PET scan receive 2 additional courses of ABVD chemotherapy in the absence of disease progression or unacceptable toxicity. Patients achieving CR, PR, or SD with a positive PET scan proceed to escalated BEACOPP chemotherapy. ESCALATED BEACOPP* CHEMOTHERAPY: Patients receive doxorubicin hydrochloride IV over 3-5 minutes and cyclophosphamide IV over 60 minutes on day 1, etoposide IV over 45-60 minutes on days 1-3, procarbazine orally (PO) on days 1-7, prednisone PO on days 1-14, and bleomycin sulfate IV and vincristine IV on day 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Within 4-6 weeks after completion of BEACOPP chemotherapy, patients undergo involved-field radiotherapy (IFRT) 5 days a week for 3½ weeks. NOTE: * HIV-positive patients receive standard BEACOPP instead of escalated BEACOPP. Patients undergo fludeoxyglucose F^18 PET/CT scan at baseline, and within 8-10 days after completion of chemotherapy. Patients also undergo additional PET/CT scans within 3-4 weeks after completion of ABVD or within 12 weeks after completion of BEACOPP and IFRT. Patients with a negative PET scan proceed to follow up. Patients with a positive PET scan undergo 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 biopsy is neither clinically appropriate nor medically feasible proceed to follow-up. Patients for whom biopsy is neither clinically indicated nor medically appropriate undergo a repeat PET/CT scan after 3 months. If PET/CT scan remains positive, patients undergo biopsy as above. After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 2-3 years, and then annually for a maximum of 5 years.

Official Title
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Phase II Trial of Response-Adapted Chemotherapy Based on Positron Emission Tomography for Non-Bulky Stage I and II Hodgkin Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: Bleomycin Sulfate
* Drug: Doxorubicin Hydrochloride
* Drug: Procarbazine Hydrochloride
* Drug: Vinblastine Sulfate
* Drug: Dacarbazine
* Drug: Cyclophosphamide
* Drug: Etoposide phosphate
* Drug: prednisone
* Drug: Radiation Therapy
* Radiation: Fludeoxyglucose F-18
* Procedure: computed tomography
* Procedure: Positron Emission Tomography


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed* Hodgkin lymphoma Clinical stage IA, IB, IIA, or IIB disease according to the modified Ann Arbor Staging Classification system Subclassified according to the WHO modification of the Rye Classification E extension allowed provided all other criteria have been met NOTE: *Pathology materials must be submitted within 60 days of study registration. Core-needle biopsies are acceptable provided they contain adequate tissue for primary diagnosis and immunophenotyping. Fine-needle aspirates not allowed. If multiple specimens are available, submit the most recent. No nodular lymphocyte-predominant Hodgkin lymphoma No mediastinal mass > 0.33 maximum intrathoracic diameter by standing postero-anterior chest x-ray or peripheral or retroperitoneal adenopathy > 10 cm in its largest diameter Measurable disease by physical examination or imaging studies Any tumor mass measurable in two dimensions and > 1 cm (or 1.5 cm if 0.5 cm slices are used, as in spiral CT scans) allowed Lesions that are considered intrinsically non-measurable include: Bone lesions Leptomeningeal disease Ascites 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 PATIENT CHARACTERISTICS: Performance status 0-2 ANC ≥ 1,000/μL Platelet count ≥ 100,000/μL Serum creatinine ≤ 2 mg/dL Bilirubin ≤ 2 mg/dL AST ≤ 2 times upper limit of normal LVEF normal by ECHO or MUGA DLCO ≥ 60% with no symptomatic pulmonary disease Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Patients with known HIV allowed provided they have CD4 counts ≥ 350/mcL Patients must not have multi-drug resistant HIV infections (i.e., concurrent AIDS-defining conditions) An HIV test is required for patients with a history of IV drug abuse or any behavior associated with an increased risk of HIVinfection No currently active second malignancy other than nonmelanoma skin cancers Patients are not considered to have a currently active malignancy provided they have completed therapy and are considered by their physician to be at < 30% risk of relapse PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemotherapy or radiotherapy for Hodgkin lymphoma 1 course of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) allowed and will be considered the first course

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (chemotherapy and F-18 PET/CT)<br>See Detailed Description | Biological: Bleomycin Sulfate<br>* Given IV<br>Drug: Doxorubicin Hydrochloride<br>* Given IV<br>Drug: Procarbazine Hydrochloride<br>* Given PO<br>Drug: Vinblastine Sulfate<br>* Given IV<br>Drug: Dacarbazine<br>* Given IV<br>Drug: Cyclophosphamide<br>* Given IV<br>Drug: Etoposide phosphate<br>* Given IV<br>Drug: prednisone<br>* Given PO<br>Drug: Radiation Therapy<br>* Undergo radiation therapy<br>Radiation: Fludeoxyglucose F-18<br>* Undergo FDG PET/CT<br>Procedure: computed tomography<br>* Undergo FDG PET/CT<br>Procedure: Positron Emission Tomography<br>* Undergo FDG PET/CT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) at 36-Months for Patients Who Received 4 Cycles of ABVD | The primary objective of this trial is to estimate the 3 year PFS in patients who received 4 cycles of ABVD. PFS for each patient is measured as the time from registration on trial to the first incident of death or progression. The PFS at 36 months is calculated as the number of patients who have a progression-free survival time greater than 36 months divided by the total number of patients that started treatment. For this endpoint, all patients that received 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) are included. | 36 Months | 
| 36 Month Progression Free Survival Rate of Patients Receiving 4 Cycles of ABVD Versus Patients Receiving 2 Cycles of ABVD and 2 Cycles of BEACOPP and Radiation. | All patients received an initial 2-28 day cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) on Days 1 and 15. After the first 2 cycles of ABVD, PET/CT was performed and submitted for central review (cycle 2, days 23-25) and determined whether patients would receive 2 cycles of escalated BEACOPP and involved-field RT (IFRT) or an additional 2 cycles of ABVD. PFS for each patient is measured as the time from registration on trial to the first incident of death or progression. The PFS rate at 36 months is calculated as the number of patients who have a progression-free survival time greater than 36 months divided by the total number of patients that started treatment. For this endpoint, we compare the PFS rate between patients who received 4 cycles of ABVD and patients who received 2 cycles of ABVD and 2 cycles of IFRT. | at 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Rate | A Complete Response (CR) was defined as having the following conditions: 1. A complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. 2. In patients with a PET scan that was positive before therapy, a post-treatment residual mass of any size is permitted as long as it is PET-negative. A Complete Response rate was defined as the number of patients who achieved a CR divided by the number of patients that were eligible for analysis in each group. The CR rate was calculated for patients that completed 4 cycles of ABVD and for patients that completed 2 cycles of ABVD and 2 cycles of BEACOPP and IFRT. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma