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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01132807
• Other study ID #: CALGB-50604
• Secondary ID: CALGB-50604NCI-2
• Status: Completed
• Phase: Phase 2
• Start date: May 2010
• Est. completion date: January 2018

Study information

• Verified date: June 2021
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: January 2018
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma

Intervention

Biological:
• Bleomycin Sulfate
Given IV

Drug:
• Doxorubicin Hydrochloride
Given IV
• Procarbazine Hydrochloride
Given PO
• Vinblastine Sulfate
Given IV
• Dacarbazine
Given IV
• Cyclophosphamide
Given IV
• Etoposide phosphate
Given IV
• prednisone
Given PO
• Radiation Therapy
Undergo radiation therapy

Radiation:
• Fludeoxyglucose F-18
Undergo FDG PET/CT

Procedure:
• computed tomography
Undergo FDG PET/CT
• Positron Emission Tomography
Undergo FDG PET/CT

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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