Response-Based Therapy Assessed By PET Scan in Treating Patients With Bulky Stage I and Stage II Classical Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Alliance for Clinical Trials in Oncology
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology ( Cancer and Leukemia Group B )
ClinicalTrials.gov Identifier:
NCT01118026
First received: May 5, 2010
Last updated: October 7, 2013
Last verified: June 2013
  Purpose

RATIONALE: 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 chemotherapy together with radiation therapy may kill more cancer cells. Diagnostic procedures, such as PET scan, done before, during, and after chemotherapy may help doctors plan the best treatment.

PURPOSE: This phase II clinical trial is studying how well response-based therapy assessed by PET scan works in treating patients with bulky stage I and stage II Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma
Biological: bleomycin sulfate
Drug: ABVD regimen
Drug: BEACOPP regimen
Drug: cyclophosphamide
Drug: dacarbazine
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: prednisone
Drug: procarbazine hydrochloride
Drug: vinblastine sulfate
Drug: vincristine sulfate
Other: laboratory biomarker analysis
Procedure: computed tomography
Radiation: fludeoxyglucose F 18
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Response-Adapted Therapy Based on Positron Emission Tomography (PET) for Bulky Stage I and Stage II Classical Hodgkin Lymphoma (HL)

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Progression-free survival at 36 months from enrollment [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete response rate [ Time Frame: Up to 8 weeks ] [ Designated as safety issue: No ]
  • Standard uptake values (SUVs) for target sites measured at baseline, after course 2, and after completion of therapy [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Determination of the optimal cutoff for absolute decrease in maximum SUV body weight (SUVbw) and SUV lean body mass (SUVlbm), relative uptake in tumor vs various reference anatomic sites, IHP criteria as well as various cutoffs for post-therapy maxim ... [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Volumetric vs 2-dimensional (2-D) measurement changes for target lesions between baseline and after course 2, at the end of chemotherapy, and after IFRT [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Comparison of qualitative and semiquantitative fludeoxyglucose-PET findings/changes, 2-D and volumetric CT changes, and combinatorial analyses (PET + dedicated CT data) with molecular parameters and conventional parameters [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 123
Study Start Date: September 2010
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:

OBJECTIVES:

Primary

  • To determine the progression-free survival (PFS) at 36 months from enrollment of patients with bulky stage I or II Hodgkin lymphoma treated with ABVD alone or followed by escalated BEACOPP and involved-field radiation therapy.

Secondary

  • To evaluate the complete response rate in patients diagnosed with bulky stage I and II Hodgkin lymphoma following PET-response-adapted chemotherapy with or without radiotherapy.
  • To determine the predictive value of semiquantitative evaluation of fludeoxyglucose (FDG) uptake using various semiquantitative approaches at baseline, after 2 courses of ABVD, and after completion of therapy.
  • To determine the predictive value of volumetric vs 2-dimensional (2-D) measurement changes on CT scan between baseline and after 2 courses, at the end of chemotherapy (PET negative patients only), and after radiotherapy (PET positive patients only), and compare with PET parameters.
  • To determine if changes in both qualitative and semiquantitative FDG-PET findings/changes between baseline and after course 2, at the end of chemotherapy (PET negative patients only), and after radiotherapy (PET positive patients only) with combination analyses incorporating changes obtained from dedicated CT scans, correlates with response and PFS.
  • To compare the predictive value of both qualitative and semiquantitative FDG-PET changes, 2-D and volumetric CT changes, and combinatorial analyses (PET + dedicated CT data) with molecular parameters and conventional parameters, including International Prognostic Score.
  • To assess whether elevated baseline serum soluble CD30 (sCD30), IL10, CCL17, and CCL22 correlate with clinical response and PFS.
  • To assess whether persistent or recurrent elevation of serial serum sCD30, IL10, CCL17, or CCL22 correlate with relapse/progression or PET scan results.
  • To confirm independently useful tissue biomarkers (bcl-2, MAL, FOXP3, GzB) for risk stratification in patients with bulky stage I or II Hodgkin lymphoma treated with this regimen.

OUTLINE: This is a multicenter study.

  • ABVD chemotherapy: All patients receive doxorubicin hydrochloride IV over 3-5 minutes, bleomycin sulfate IV, 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 in the absence of disease progression or unacceptable toxicity. Patients then undergo a PET/CT scan and CT scan of the neck (if it was positive at baseline), chest, abdomen, and pelvis. Patients who are PET-positive proceed to escalated BEACOPP chemotherapy. Patients who are PET-negative receive 4 additional courses of ABVD chemotherapy in the absence of disease progression or unacceptable toxicity.
  • Escalated BEACOPP chemotherapy: Patients receive doxorubicin hydrochloride IV over 3-5 minutes and cyclophosphamide IV over 60 minutes on day 1; etoposide IV over 60 minutes on days 1, 2, and 3; oral procarbazine hydrochloride once daily on days 1-7; oral prednisone on days 1-14; and bleomycin sulfate IV and vincristine sulfate IV on day 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo another PET/CT scan and CT scan of the neck (if it was positive at baseline), chest, abdomen, and pelvis. Patients then undergo involved-field radiation therapy 5 days per week for 3½ weeks (for a total of 30.6 Gy).

Within 3-8 weeks after completion of chemotherapy, patients undergo an additional PET/CT scan (utilizing fludeoxyglucose F 18) and CT scan of the neck (if it was positive at baseline), chest, abdomen, and pelvis. Patients who are PET-negative proceed to follow up. Patients who are PET-positive undergo a 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 a biopsy is neither clinically appropriate nor medically feasible proceed to follow up. Patients who defer the biopsy undergo scanning 3 months later and then undergo biopsy as above.

Blood and serum samples may be collected periodically for biomarker and IHC analysis.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2 years, and then annually for 7 years.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
    • Patients with "E" extensions are eligible provided all other criteria have been met NOTE: *Patients must submit pathology materials within 60 days of study registration. Core-needle biopsies are acceptable provided they contain adequate tissue for primary diagnosis and immunophenotyping. Fine-needle aspirates are not acceptable. If multiple specimens are available, submit the most recent.
  • No nodular lymphocyte-predominant Hodgkin lymphoma
  • Has a mediastinal mass > 0.33 maximum intrathoracic diameter on standing postero-anterior chest x-ray or measuring > 10 cm in its largest diameter

PATIENT CHARACTERISTICS:

  • Performance status 0-2
  • ANC ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Serum creatinine ≤ 2 mg/dL
  • Bilirubin ≤ 2 times upper limit of normal (ULN) (in the absence of Gilbert disease)
  • AST ≤ 2 times ULN
  • LVEF by ECHO or MUGA normal (unless thought to be disease-related)
  • DLCO ≥ 60% with no symptomatic pulmonary disease (unless thought to be disease-related)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No "currently active" second malignancy other than nonmelanoma skin cancers

    • Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at < 30% risk of relapse
  • Patients with known HIV are eligible provided their CD4 count is > 350, and they are on concurrent antiretrovirals

    • An HIV test is required for patients with a history of IV drug abuse or any behavior associated with an increased risk of HIV

PRIOR CONCURRENT THERAPY:

  • No prior treatment (chemotherapy or radiotherapy) for Hodgkin lymphoma
  • No concurrent zidovudine or stavudine as part of the antiretroviral therapy for HIV-positive patients
  • No concurrent hormones or other chemotherapeutic agents, except for the following:

    • Steroids for adrenal failure
    • Hormones for non-disease-related conditions (e.g., insulin for diabetes)
    • Dexamethasone on the day of chemotherapy for (acute) chemotherapy-induced nausea or vomiting
  • No concurrent intensity-modulated radiation therapy or cobalt-60
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01118026

Locations
United States, Delaware
CCOP - Christiana Care Health Services Recruiting
Newark, Delaware, United States, 19713
Contact: Clinical Trial Office - CCOP - Christiana Care Health Services    302-623-4450      
United States, District of Columbia
MedStar Georgetown University Hospital Recruiting
Washington, District of Columbia, United States, 20007
Contact: Bruce Cheson    202-444-7932      
United States, Illinois
University of Chicago Cancer Research Center Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Clinical Trials Office - University of Chicago Cancer Research    773-834-7424      
Evanston Hospital Recruiting
Evanston, Illinois, United States, 60201-1781
Contact: Clinical Trials Office - Evanston Hospital    847-570-1381      
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Clinical Trials Office - Greenebaum Cancer Center at Universit    800-888-8823      
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Ann S. LaCasce, MD    617-632-5959      
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Clinical Trials Office - Massachusetts General Hospital    877-726-5130      
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Nancy L. Bartlett, MD    314-362-5654      
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Nancy Bartlett    314-362-5654      
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-6805
Contact: Clinical Trials Office - UNMC Eppley Cancer Center at the Univ    800-999-5465      
United States, New Hampshire
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03756-0002
Contact: Clinical Trials Office - Norris Cotton Cancer Center    603-650-7609    cancerhelp@dartmouth.edu   
United States, New York
New York Weill Cornell Cancer Center at Cornell University Recruiting
New York, New York, United States, 10021
Contact: Clinical Trials Office - New York Weill Cornell Cancer Center    212-746-1848      
SUNY Upstate Medical University Hospital Recruiting
Syracuse, New York, United States, 13210
Contact: Clinical Trials Office - SUNY Upstate Medical University Hospi    315-464-5476      
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center Recruiting
Charlotte, North Carolina, United States, 28232-2861
Contact: Clinical Trials Office - Blumenthal Cancer Center at Carolinas    704-355-2884      
Carolinas Medical Center/Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28206
Contact: David Miller    980-442-5221      
Presbyterian Hospital Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Mark Mogul    304-399-6503      
Batte Cancer Center at Northeast Medical Center Recruiting
Concord, North Carolina, United States, 28025
Contact: David W. Miller, MD    704-302-8300      
Wayne Memorial Hospital, Incorporated Recruiting
Goldsboro, North Carolina, United States, 27534
Contact: James N. Atkins, MD    919-580-0000      
Iredell Memorial Hospital Recruiting
Statesville, North Carolina, United States, 28677
Contact: Ruby Grimm    704-873-2219      
Wake Forest University Health Sciences Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: David Hurd    336-716-2088      
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Ohio State University Cancer Clinical Trial Matching Service    866-627-7616    Jamesline@osumc.edu   
United States, Vermont
Central Vermont Medical Center/National Life Cancer Treatment Recruiting
Berlin, Vermont, United States, 05602
Contact: Emiliano Mugnaini    802-656-5487      
Fletcher Allen Health Care - University Health Center Campus Recruiting
Burlington, Vermont, United States, 05401
Contact: Clinical Trials Office - Fletcher Allen Health Care    802-656-8990      
United States, Virginia
Virginia Commonwealth University Massey Cancer Center Recruiting
Richmond, Virginia, United States, 23298-0037
Contact: Clinical Trials Office -Virginia Commonwealth University Masse    804-628-1939      
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Principal Investigator: Ann S. LaCasce, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology ( Cancer and Leukemia Group B )
ClinicalTrials.gov Identifier: NCT01118026     History of Changes
Other Study ID Numbers: CALGB-50801, CDR0000669076, NCI-2011-02034
Study First Received: May 5, 2010
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma
adult favorable prognosis Hodgkin lymphoma
adult lymphocyte depletion Hodgkin lymphoma
adult lymphocyte predominant Hodgkin lymphoma
adult mixed cellularity Hodgkin lymphoma
adult nodular sclerosis Hodgkin lymphoma
adult unfavorable prognosis Hodgkin lymphoma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bleomycin
Doxorubicin
Liposomal doxorubicin
Cyclophosphamide
Dacarbazine
Etoposide
Prednisone
Procarbazine
Vinblastine
Vincristine
Fluorodeoxyglucose F18
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014