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

Tracking Information
First Submitted Date ICMJE	May 27, 2010
First Posted Date ICMJE	May 28, 2010
Last Update Posted Date	January 24, 2018
Study Start Date ICMJE	May 2010
Actual Primary Completion Date	February 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 17, 2015)	Progression-free survival (PFS) at 36 months [ Time Frame: 36 months ]
Original Primary Outcome Measures ICMJE; (submitted: May 27, 2010)	Progression-free survival (PFS) at 36 months; PFS after 2 courses of ABVD
Change History	Complete list of historical versions of study NCT01132807 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 23, 2015)	complete response rate [ Time Frame: Up to 5 years ]
Original Secondary Outcome Measures ICMJE; (submitted: May 27, 2010)	Complete response rate; FDG/PET uptake; Volumetric changes on CT scan after courses 2 and 4 of ABVD; Changes in metabolic parameters
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Chemotherapy Based on Positron Emission Tomography Scan in Treating Patients With Stage I or Stage II Hodgkin Lymphoma
Official Title ICMJE	Phase II Trial of Response-Adapted Chemotherapy Based on Positron Emission Tomography for Non-Bulky Stage I and II Hodgkin Lymphoma
Brief Summary	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	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.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Lymphoma
Intervention ICMJE	Biological: Bleomycin Sulfate Given IV; Drug: Doxorubicin Hydrochloride Given IV; Drug: Procarbazine Hydrochloride Given PO; Drug: Vinblastine Sulfate Given IV; Drug: Dacarbazine Given IV; Drug: Cyclophosphamide Given IV; Drug: Etoposide phosphate Given IV; Drug: prednisone Given PO; Drug: Radiation Therapy Undergo radiation therapy; Radiation: Fludeoxyglucose F-18 Undergo FDG PET/CT; Procedure: computed tomography Undergo FDG PET/CT; Procedure: Positron Emission Tomography Undergo FDG PET/CT
Study Arms	Experimental: Treatment (chemotherapy and F-18 PET/CT); See Detailed Description; Interventions: 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
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 11, 2017)	164
Original Estimated Enrollment ICMJE; (submitted: May 27, 2010)	149
Actual Study Completion Date	January 2018
Actual Primary Completion Date	February 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 60 Years (Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01132807
Other Study ID Numbers ICMJE	CALGB-50604; CALGB-50604; NCI-2011-02042 ( Registry Identifier: NCI Clinical Trial Reporting Program ); U10CA180821 ( U.S. NIH Grant/Contract ); CDR0000672913 ( Registry Identifier: NCI Physician Data Query )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Alliance for Clinical Trials in Oncology
Study Sponsor ICMJE	Alliance for Clinical Trials in Oncology
Collaborators ICMJE	National Cancer Institute (NCI)
Investigators ICMJE	Principal Investigator: David J. Straus, MD Memorial Sloan Kettering Cancer Center
PRS Account	Alliance for Clinical Trials in Oncology
Verification Date	January 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP