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Study Summary
No. SWOG S0816:.......Lymphoma......Michelle A. Fanale......Lymphoma/Myeloma
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Study Summary Title
Study Summary
Number:
SWOG S0816
Study Title:A Phase II Trial of Response-Adapted Therapy of Stage III/IV Hodgkin Lymphoma Using Early Interim FDG-PET Imaging
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Physician New Patient Referral
Name:Michelle A. FanalePatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Lymphoma/MyelomaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2860
Contact us about clinical trials
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General Information
Disease Group:LymphomaSupported By:Southwest Oncology Group
Phase of Study:Phase IIReturn
Visit:
Screening; D1, D15, D29, D43, D53, D57, D71, D 78, D85, D99, D113, D120, D127,
D141, D155, D162, D186, D190, D276, D365
Treatment
Agents:
Adriamycin
Bleomycin
Cyclophosphamide
Dacarbazine
Doxorubicin
Etoposide
FDGPET)
None
Prednisone
Procarbazine
Vincristine
Vincristine Sulfate
Home Care:N/A
Treatment Loc:Both at MDACC & Community Programs (CCOP/Network)
Estimated
Length of Stay
in Houston:
none
Description/
Intervention:
The goal of this clinical research study is to find out if switching from a
standard chemotherapy combination to a more intensive experimental combination,
based on imaging scans, will improve response to treatment in patients with
Hodgkin lymphoma (HL). The safety of this experimental chemotherapy
combination will also be studied.
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Study Objectives / Outcomes
The co-primary objectives are:

1a. To estimate the 2-year progression-free survival (PFS) in human immunodeficiency virus (HIV)-negative patients with
advanced stage Hodgkin Lymphoma (HL) treated with response-adapted therapy based on FDG-PET imaging after 2 cycles
of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD).

1b. To estimate the 2-year PFS in the subset of HIV-negative patients with advanced stage HL who are PET-positive after 2
cycles of ABVD and are subsequently treated with escalated dose BEACOPP (Bleomycin, Etoposide, Adriamycin,
Cyclophosphamide, Vincristine, Procarbazine, and Prednisone).

Secondary objectives include:

1. To estimate the 2-year overall survival (OS) for HIV-negative patients treated with response- adapted therapy.

2. To estimate the response rate (complete and partial) for HIV-negative patients treated with response- adapted therapy.

3. To evaluate the toxicity of this response-adapted regimen.

4. To document the feasibility of centralized, real-time review of 2-Deoxy-2- [18F]fluoro-D-Glucose positron emission
tomography FDG-PET imaging for U.S. cooperative group studies.

5. To prospectively evaluate the overall response rate, complete response rate, PFS, and OS of a cohort of HIV-positive
patients with HL treated with response-adapted therapy. The use of cycle-2 PET scanning in HIV infection will be done to
provide preliminary data for this strategy in HIV-infected patients.

6. To prospectively identify serum and tissue biomarkers associated with progression-free and overall survival of patients with HL treated with response-adapted therapy. Biologic features meriting specific investigation include the degree of tumor cell infiltration with Tregulatory cells, the FOXP3/Granzyme B ratio, and the expression of micro architectural level (MAL) or Bcl-2 in biopsy samples, and Thymus and Activation Regulated Chemokine (TARC) levels in serum specimens.

7.To prospectively evaluate HIV viral load and CD4 cells in the cohort of HIV-positive patients with HL treated with response-adapted therapy.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:12/03/2009
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:300
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) All patients must have previously untreated Stage III or IV classical Hodgkin lymphoma (nodular sclerosing, mixed cellularity, lymphocyte-rich, or lymphocyte depleted). Nodular lymphocyte predominant Hodgkin Lymphoma is not eligible. All histology will be reviewed centrally.

2) Pathology Review: Adequate sections and a paraffin block from the original diagnostic specimen must be available for submission for review by the lymphoma pathology group. If the entire paraffin block cannot be sent, cores or punches from these blocks are acceptable. An adequate biopsy requires sufficient tissue to establish the architecture and a WHO histologic subtype with certainty. Thus, core biopsies, especially multiple core biopsies MAY be adequate; whereas, needle aspirations or cytologies are not adequate. Specimen submission is not a requirement for participation in the study.

3) Patients must be offered the opportunity to consent to the correlative science studies. Patients are encouraged to submit tissue and serum for the correlative science studies; however, specimen submission is not a requirement for participation in the study.

4) Patients must be age 18-60. This is due to concerns about the toxicity of BEACOPP regimen in patients over the age of 60.

5) All patients must have bidimensionally measurable disease documented on the Lymphoma Baseline Tumor Assessment Form within 28 days prior to registration. Patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed with 42 days prior to registration.

6) Patients must have a unilateral or bilateral bone marrow biopsy performed within 42 days prior to registration.

7) Patients must have a diagnostic quality 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 Positron Emission Tomograpy/CAT scan (PET/CT) are not adequate for enrollment or response determination on this protocol.

8) continued from number 7. However, if the CT scan of a PET/CT hybrid is performed with both oral and IV contrast with contrast enhancement in the arterial and/or portal venous phase, is at least a 2-slice CT, is acquired with at least 80 mAs and CT scans are obtained with contiguous sections, with a maximum of 5 mm slice thickness, then the pre-treatment and any posttherapy PET/CT scan alone will suffice for patients enrolled on this trial.

9) Patients must not have received prior chemotherapy, radiation, or antibody therapy for lymphoma.

10) Patients must have a Zubrod performance status of 0 - 2.

11) Serum erythrocyte sedimentation rate (ESR), lactic dehydrogenase (LDH), hemoglobin, albumin, white blood cell (WBC), and lymphocytes must be measured within 28 days prior to registration.

12) Serum estradiol (women only), testosterone (men only), FSH and LH (both men and women) levels must be drawn within 60 days prior to registration, to obtain baseline values.

13) Patients with a history of hypertension or cardiac symptoms must have a Multi-gated Acquisition (MUGA) scan or an echocardiogram (ECHO) with no significant abnormalities and a cardiac ejection fraction >= 45% within 42 days prior to registration.

14) Patients must not be sero-positive for Hepatitis B (Hepatitis B surface antigen positive or anti-hepatitis B core antigen positive) or sero-positive for Hepatitis C (anti-Hepatitis C antibody positive). However, patients who are immune to hepatitis B (anti-Hepatitis B surface antibody positive) are eligible (e.g. patients immunized against hepatitis B).

15) Patient HIV status must be known prior to registration. HIV-positive patients must not have multi-drug resistant HIV infection, CD4 counts < 150/mcL or other concurrent AIDS defining conditions. HIV-positive patients are eligible if they have CD4 counts >= 150/mcL at the time of enrollment OR if they had a documented CD4 count > 250 at any time within 8 months prior to HL diagnosis, but will be analyzed separately in an independent cohort.

16) Patients must not have significant lung disease with abnormal lung function tests (Diffusing Capacity of the Lung for Carbon Monoxide [DLCO] > 25% below predicted after correction for hemoglobin) unless it is attributable to lymphoma. Patients must not be requiring continuous supplemental oxygen therapy.

17) Patients must not have had prior solid organ transplantation.

18) 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.

19) 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. 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

20) 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.

21) At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base.

22) For second registration: Patients must have completed 2 cycles of ABVD with no evidence of disease progression.

23) For second registration: Baseline and interim PET/CT scans must have been submitted promptly for centralized review to the Cancer And Leukemia Group B Imaging Core Laboratory (CALGB ICL).

24) For second registration: Patients must be planning to begin either continued ABVD or BEACOPP (escalated dose for HIV-negative patients, standard for HIV-positive patients) within 10 days after interim PET/CT.

Exclusion Criteria:N/A

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Links
Registration Number: NCT00822120
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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