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

Phase 2

Completed

Conditions: Lymphoma

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

Registration Number: NCT01132807

Lead Sponsor: Alliance for Clinical Trials in Oncology

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 164

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (chemotherapy and F-18 PET/CT)	Radiation Therapy	See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)	Positron Emission Tomography	See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)	Bleomycin Sulfate	See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)	Procarbazine Hydrochloride	See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)	Vinblastine Sulfate	See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)	Etoposide phosphate	See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)	computed tomography	See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)	Fludeoxyglucose F-18	See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)	Dacarbazine	See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)	Doxorubicin Hydrochloride	See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)	prednisone	See Detailed Description
Treatment (chemotherapy and F-18 PET/CT)	Cyclophosphamide	See Detailed Description

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) at 36-Months for Patients Who Received 4 Cycles of ABVD	36 Months	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 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.	at 36 months	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.

Secondary Outcome Measures

Name	Time	Method
Complete Response Rate	Up to 5 years	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.

Trial Locations

Locations (95): Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
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Wilkes-Barre, Pennsylvania, United States
UMASS Memorial Cancer Center - University Campus
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Worcester, Massachusetts, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Baltimore, Maryland, United States
SUNY Upstate Medical University Hospital
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Syracuse, New York, United States
Fletcher Allen Health Care - University Health Center Campus
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Burlington, Vermont, United States
CCOP - Upstate Carolina
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Spartanburg, South Carolina, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
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Columbus, Ohio, United States
Louis A. Weiss Memorial Hospital
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Chicago, Illinois, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
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Chicago, Illinois, United States
John H. Stroger, Jr. Hospital of Cook County
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Chicago, Illinois, United States
University of Chicago Cancer Research Center
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Chicago, Illinois, United States
Case Comprehensive Cancer Center
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Cleveland, Ohio, United States
University Medical Center of Southern Nevada
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Las Vegas, Nevada, United States
Mount Sinai Hospital Medical Center
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Chicago, Illinois, United States
Lucille P. Markey Cancer Center at University of Kentucky
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Lexington, Kentucky, United States
CCOP - Christiana Care Health Services
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Newark, Delaware, United States
Evanston Hospital
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Evanston, Illinois, United States
Siouxland Hematology-Oncology Associates, LLP
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Sioux City, Iowa, United States
CCOP - North Shore University Hospital
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Manhasset, New York, United States
Castle Medical Center
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Kailua, Hawaii, United States
Arizona Cancer Center at University of Arizona Health Sciences Center
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Tucson, Arizona, United States
Oncare Hawaii, Incorporated - Pali Momi
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'Aiea, Hawaii, United States
McFarland Clinic, PC
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Ames, Iowa, United States
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
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Washington, District of Columbia, United States
Decatur Memorial Hospital Cancer Care Institute
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Decatur, Illinois, United States
Greenebaum Cancer Center at University of Maryland Medical Center
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Baltimore, Maryland, United States
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
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Boston, Massachusetts, United States
MBCCOP - Medical College of Georgia Cancer Center
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Augusta, Georgia, United States
Cardinal Bernardin Cancer Center at Loyola University Medical Center
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Maywood, Illinois, United States
Mary Bird Perkins Cancer Center - Baton Rouge
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Baton Rouge, Louisiana, United States
CancerCare of Maine at Eastern Maine Medical Center
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Bangor, Maine, United States
City of Hope Comprehensive Cancer Center
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Duarte, California, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
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Saint Louis, Missouri, United States
West Michigan Cancer Center
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Kalamazoo, Michigan, United States
CCOP - Duluth
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Duluth, Minnesota, United States
CCOP - Wichita
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Wichita, Kansas, United States
St. Charles Mercy Hospital
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Oregon, Ohio, United States
Regions Hospital Cancer Care Center
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Saint Paul, Minnesota, United States
Iredell Memorial Hospital
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Statesville, North Carolina, United States
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
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Spartanburg, South Carolina, United States
Harrington Cancer Center
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Amarillo, Texas, United States
Missouri Baptist Cancer Center
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Saint Louis, Missouri, United States
Hickman Cancer Center at Bixby Medical Center
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Adrian, Michigan, United States
New York Weill Cornell Cancer Center at Cornell University
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New York, New York, United States
Presbyterian Cancer Center at Presbyterian Hospital
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Charlotte, North Carolina, United States
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
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Madison, Wisconsin, United States
Fox Chase Cancer Center CCOP Research Base
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Philadelphia, Pennsylvania, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
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Dallas, Texas, United States
Billings Clinic - Downtown
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Billings, Montana, United States
Marshfield Clinic - Indianhead Center
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Rice Lake, Wisconsin, United States
Long Island Jewish Medical Center
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New Hyde Park, New York, United States
Center for Cancer Treatment & Prevention at Sacred Heart Hospital
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Eau Claire, Wisconsin, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
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Lebanon, New Hampshire, United States
Cleveland Clinic Taussig Cancer Center
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Cleveland, Ohio, United States
West Tennessee Cancer Center at Jackson-Madison County General Hospital
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Jackson, Tennessee, United States
Vanderbilt-Ingram Cancer Center
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Nashville, Tennessee, United States
Kapiolani Medical Center at Pali Momi
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'Aiea, Hawaii, United States
Kauai Medical Clinic
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Lihue, Hawaii, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
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Rochester, New York, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
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Omaha, Nebraska, United States
Saint Michael's Hospital Cancer Center
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Stevens Point, Wisconsin, United States
Union Hospital of Cecil County
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Elkton, Maryland, United States
Humphrey Cancer Center at North Memorial Outpatient Center
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Robbinsdale, Minnesota, United States
Don Monti Comprehensive Cancer Center at North Shore University Hospital
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Manhasset, New York, United States
Memorial Sloan-Kettering Cancer Center
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New York, New York, United States
Blumenthal Cancer Center at Carolinas Medical Center
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Charlotte, North Carolina, United States
Monter Cancer Center of the North Shore-LIJ Health System
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Lake Success, New York, United States
Wayne Memorial Hospital, Incorporated
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Goldsboro, North Carolina, United States
Bon Secours St. Francis Health System
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Greenville, South Carolina, United States
Mountainview Medical
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Berlin, Vermont, United States
Geisinger Cancer Institute at Geisinger Health
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Danville, Pennsylvania, United States
Toledo Clinic, Incorporated - Main Clinic
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Toledo, Ohio, United States
University Cancer Center at University of Washington Medical Center
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Seattle, Washington, United States
Marshfield Clinic - Lakeland Center
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Minocqua, Wisconsin, United States
Diagnostic and Treatment Center
🇺🇸
Weston, Wisconsin, United States
Saint Joseph's Hospital
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Marshfield, Wisconsin, United States
Mary Babb Randolph Cancer Center at West Virginia University Hospitals
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Morgantown, West Virginia, United States
Gundersen Lutheran Center for Cancer and Blood
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La Crosse, Wisconsin, United States
Marshfield Clinic - Marshfield Center
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Marshfield, Wisconsin, United States
Ministry Medical Group at Saint Mary's Hospital
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Rhinelander, Wisconsin, United States
M.D. Anderson Cancer Center at Orlando
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Orlando, Florida, United States
Louisville Oncology at Norton Cancer Institute - Louisville
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Louisville, Kentucky, United States
Wake Forest University Comprehensive Cancer Center
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Winston-Salem, North Carolina, United States
Norton Suburban Hospital
🇺🇸
Louisville, Kentucky, United States
Saint Joseph Mercy Cancer Center
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Ann Arbor, Michigan, United States
Yale Cancer Center
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New Haven, Connecticut, United States
MBCCOP - LSU Health Sciences Center
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New Orleans, Louisiana, United States
Medical Center of Louisiana - New Orleans
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New Orleans, Louisiana, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸
Richmond, Virginia, United States
OnCare Hawaii, Incorporated - Lusitana
🇺🇸
Honolulu, Hawaii, United States
Queen's Cancer Institute at Queen's Medical Center
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Honolulu, Hawaii, United States
Straub Clinic and Hospital, Incorporated
🇺🇸
Honolulu, Hawaii, United States
OnCare Hawaii, Incorporated - Kuakini
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Honolulu, Hawaii, United States
Kuakini Medical Center
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Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and Children
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Honolulu, Hawaii, United States