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

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, Diagnostic, TreatmentActive18 to 60NCI, OtherCALGB-50801
CDR0000669076, NCI-2011-02034, NCT01118026

Trial Description

Summary

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.

Further Study Information

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 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

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer and Leukemia Group B

  • National Cancer Institute
Ann S. LaCasce, Principal Investigator

Trial Sites

U.S.A.

California
Saint Helena

Saint Helena Hospital

Gregory B Smith
Ph: 707-967-3698

Delaware
Newark

Helen F. Graham Cancer Center at Christiana Hospital

Stephen Scott Grubbs
Ph: 302-733-6227

Illinois
Chicago

University of Chicago Cancer Research Center

Chadi Nabhan
Ph: 773-834-7424

Evanston

CCOP - Evanston

David L. Grinblatt
Ph: 847-570-2109

Indiana
Mishawaka

Memorial Regional Cancer Center Day Road

Thomas Joseph Reid
Ph: 800-284-7370

South Bend

Memorial Hospital of South Bend

Thomas Joseph Reid
Ph: 800-284-7370

Kansas
Wichita

Cancer Center of Kansas, PA - Wichita

Shaker R. Dakhil
Ph: 316-262-4467

Via Christi Cancer Center at Via Christi Regional Medical Center

Shaker R. Dakhil
Ph: 316-262-4467

Massachusetts
Boston

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Ann S. LaCasce
Ph: 866-790-4500

Massachusetts General Hospital

Ann S. LaCasce
Ph: 866-790-4500

Missouri
Saint Louis

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

Nancy L. Bartlett
Ph: 800-600-3606
Email: info@siteman.wustl.edu

Springfield

Hulston Cancer Center at Cox Medical Center South

Jay W Carlson
Ph: 800-821-7532

St. John's Regional Health Center

Jay W Carlson
Ph: 800-821-7532

Nebraska
Omaha

Fred and Pamela Buffett Cancer Center

Philip J. Bierman
Ph: 402-559-6941
Email: unmcrsa@unmc.edu

New York
Syracuse

SUNY Upstate Medical University Hospital

Dorothy C Pan
Ph: 315-464-5476

North Carolina
Charlotte

Blumenthal Cancer Center at Carolinas Medical Center

David Weldon Miller
Ph: 704-355-2884

Presbyterian Cancer Center at Presbyterian Hospital

Justin P Favaro
Ph: 704-384-5369

Concord

Batte Cancer Center at Northeast Medical Center

David Weldon Miller
Ph: 704-355-2884

Durham

Duke Cancer Institute

Jeffrey Crawford
Ph: 888-275-3853

Goldsboro

Wayne Memorial Hospital, Incorporated

James N. Atkins
Ph: 919-580-0000

Statesville

Iredell Memorial Hospital

Ruby A. Grimm
Ph: 704-873-5661

Winston-Salem

Wake Forest University Comprehensive Cancer Center

David Duane Hurd
Ph: 336-713-6771

Ohio
Columbus

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Ann S. LaCasce

Oregon

St. Charles Mercy Hospital

Rex B Mowat
Ph: 800-444-3561

Toledo

Toledo Clinic, Incorporated - Main Clinic

Rex B Mowat
Ph: 800-444-3561

South Carolina
Greenville

Bon Secours St. Francis Health System

Charles E Bowers
Ph: 800-486-5941

Spartanburg

Gibbs Regional Cancer Center at Spartanburg Regional Medical Center

Charles E Bowers
Ph: 800-486-5941

Vermont
Berlin

Mountainview Medical

Gurpreet Lamba
Ph: 802-656-8990

Burlington

University of Vermont Cancer Center

Gurpreet Lamba
Ph: 802-656-8990

Virginia
Richmond

Virginia Commonwealth University Massey Cancer Center

Beata Holkova
Ph: 804-628-1939

Wisconsin
La Crosse

Gundersen Lutheran Center for Cancer and Blood

Kurt Oettel
Ph: 608-775-2385
Email: cancerctr@gundluth.org

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01118026
ClinicalTrials.gov processed this data on April 09, 2015

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.