Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Phase III Study of a Treatment Driven by Early PET Response Compared to a Treatment Not Monitored by Early PET in Patients With Ann Arbor Stage III-IV or High Risk IIB Hodgkin Lymphoma
Brief Summary: All study treatments have proven efficacy in the treatment in Hodgkin lymphoma (HL). It is hoped that patients will achieve a good response to both induction therapies consisting either of 4 cycles of BEACOPPesc (Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and Prednisone) or 2 cycles of BEACOPPesc plus 2 cycles of ABVD (Adriamycine, Bléomycine, Vinblastine, Décarbazine).

The use of F-FDG Position Emission Tomography performed after 2 cycles of chemotherapy (PET2) in the experimental arm will help to stratify patients in order to restrict the BEACOPPesc therapy continuation to those patients who achieved only a partial response after 2 BEACOPPesc regimen and to allow a conventional dose ABVD chemotherapy strategy for PET2 negative patients. For all patients included in the trial the achievement of a good response to induction treatment will be checked after four cycles of induction treatment including a centrally reviewed PET assessment

Patients will be randomized after verification of eligibility and before the start of the protocol treatment.Patients will be randomly assigned to the standard treatment arm not monitored by early PET, or the experimental treatment arm driven by the PET2 result.


Options:
A: 1. Documentation of Disease:

   1.1 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 biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping. Fine needle aspirate (FNA) cytologies and bone marrow biopsies as the sole means of diagnosis are not acceptable.
   * Note: Failure to submit pathology slides within 60 days of patient registration will result in patient being declared ineligible.

   1.2 Patients may not have a mediastinal mass \> 0.33 maximum intrathoracic diameter on standing postero-anterior chest x-ray or peripheral or retroperitoneal adenopathy \> 10 cm in its largest diameter.

   1.3 Bone marrow biopsy is required for pretreatment evaluation. Bilateral biopsies are preferred but not required.
2. No prior treatment (chemotherapy or radiation therapy) for Hodgkin lymphoma.
3. Measurable disease must be present either on physical examination or imaging studies. Any tumor mass measurable in two dimensions and \> 2 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
   * ascites
   * pleural/pericardial effusion
   * inflammatory breast disease
   * 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
4. Age ≥ 16 years
5. Performance status 0-2
6. LVEF by ECHO or MUGA within institutional normal limits
7. DLCO ≥ 60% with no symptomatic pulmonary disease
8. No known HIV infection. 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. Patients who test positive or who are known to be infected are not eligible due to an increased risk of infection with this chemotherapy regimen. An HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk.
9. Non-pregnant and non-lactating. 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.
10. Initial Required Laboratory Data:

    * ANC ≥ 1000/μL
    * Platelet count ≥ 100,000/μL
    * Serum Creatinine ≤ 2 mg/dL
    * Bilirubin ≤ 2 mg/dL
    * AST ≤ 2 x upper limit of normal
B: DISEASE CHARACTERISTICS:

* Histologically confirmed classical Hodgkin lymphoma (HL) meeting the following criteria:

  * Meets current WHO classification criteria (i.e., nodular sclerosis, mixed cellularity, lymphocyte rich, and lymphocyte-depleted)
  * Clinical stage IIB, III, or IV disease OR clinical stage IIA disease with adverse features, including any of the following:

    * Bulk mediastinal disease, defined as maximal transverse diameter of mass \> 0.33 of the internal thoracic diameter at D5/6 interspace on routine chest x-ray
    * Disease outside the mediastinum and lymph node or lymph node mass \> 10 cm in diameter
    * More than two sites of disease
    * Other poor-risk features that require treatment with full course combination chemotherapy
* Newly diagnosed disease
* No CNS or meningeal involvement by lymphoma

PATIENT CHARACTERISTICS:

* ECOG performance status 0-3
* Life expectancy \> 3 months
* ANC \> 1,500/mm\^3 (unless there is bone marrow infiltration by lymphoma)
* Platelet count \> 100,000/mm\^3 (unless there is bone marrow infiltration by lymphoma)
* Creatinine \< 150% of upper limit of normal (ULN)
* Bilirubin \< 2.0 times ULN (unless attributed to lymphoma)
* Transaminases \< 2.5 times ULN (unless attributed to lymphoma)
* LVEF ≥ 50% (in patients with a significant history of ischemic heart disease or hypertension)
* Diffusion capacity within 25% of normal predicted value by lung function testing
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Amenable to the administration of a full course of chemotherapy, according to the investigator
* Must have access to PET/CT scanning
* No poorly controlled diabetes mellitus
* No cardiac contraindication to doxorubicin hydrochloride, including abnormal contractility by ECHO or MUGA
* No neurological contraindication to chemotherapy (e.g., pre-existing neuropathy)
* No other concurrent uncontrolled medical condition
* No other active malignant disease within the past 10 years, except fully excised basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix
* No known positivity for HIV, hepatitis B surface antigen, or hepatitis C

  * Routine testing, in the absence of risk factors, is not required
* No medical or psychiatric condition that compromises the patient's ability to give informed consent

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy, radiotherapy or other investigational drug for HL
C: Inclusion Criteria:

* Patient with a first diagnosis of classical Hodgkin lymphoma according to world health organization (WHO) criteria excluding nodular lymphocyte predominant subtype
* Age of 16 to 60 years
* No previous treatment for Hodgkin lymphoma
* Ann Arbor stages:

IIB with mediastinum/thorax ≥0.33 or extra nodal localization III IV

* Baseline 18-FDG PET scan (PET0)(F-FDG Positon Emission Tomography) performed before any treatment with at least one hypermetabolic lesion
* Eastern Cooperative Oncology Group (ECOG) performance status \< 3
* With a minimum life expectancy of 3 months
* Having previously signed a written informed consent
* The patient must be covered by a social security system (in France)

Exclusion Criteria:

* Pregnant or lactating women
* Men and women of childbearing potential not practicing an adequate method of contraception during the study treatment and at least 3 months after the last study drug administration
* Any history of cancer or cancer treatment during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma
* Uncontrolled infectious disease, including active HBV (hepatitis B virus) infection defined by either detection of HBs Antigen or presence of anti HBs antibody without detectable anti HBc antibody.
* HIV (Human immunodeficiency virus), HCV (hepatitis C virus) or HTLV (Human T-lymphotropic virus) serology positivity
* Abnormal liver (bilirubin \> 2,5 N) function unless abnormalities are due to AHL 2011 Protocol Version n°1.2_ 09/02/11_approved on March 11, 2011 EudraCT n°2010-022844-19 4 / 73 Hodgkin lymphoma
* Abnormal renal (Creatinin \> 150 μmol/L) function unless abnormalities are due to Hodgkin lymphoma
* Leukopenia \< 2 G/l or thrombopenia \<100 G/l unless abnormalities are due to Hodgkin lymphoma
* Severe cardio-pulmonary, or metabolic disease interfering with normal application of protocol treatment:
* Left Ejection Ventricular Fraction \<50%
* Respiratory insufficiency prohibiting bleomycin use
* Uncontrolled diabetes mellitus leading to impossibility to perform PET scan
* Impossibility to perform a baseline PET (PET0) before randomization and treatment beginning
* Incapable person
D: Inclusion Criteria:

* Hodgkin´s lymphoma (histologically proven)
* CS (PS) IA, IB, IIA,IIB without any of the following risk factors:

  1. bulky mediastinal mass (\> 1/3 maximum transverse thorax diameter)
  2. extranodal involvement
  3. ESR \> 50 (A), \> 30 (B-symptoms)
  4. 3 or more lymph node areas involved
* written informaed consent

Exclusion Criteria:

* Leukocytes \<3000/microl
* Platelets \<100000/microl
* Hodgkin´s Disease as "composite lymphoma"
* Activity index (WHO) \< grade 2

Answer: C