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

NCT ID: NCT01118026

Last Updated: 2021-12-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2021-09-29

Brief Summary

This research is being done in order to improve treatment outcomes in patients diagnosed with bulky, early stage Hodgkin lymphoma and to reduce the side effects that are associated with use of radiation used in current treatments. The chemotherapy treatment in this study consists of a combination of four drugs approved by the Food and Drug Administration (FDA): doxorubicin, bleomycin, vinblastine, and dacarbazine. This regimen (called ABVD) has been found to be effective in treating patients with Hodgkin lymphoma and is considered the standard of treatment used with radiation therapy in patients with bulky early stage Hodgkin lymphoma. As part of the evaluation of the effectiveness of the chemotherapy treatment, PET scans will be obtained during the course of therapy. The usefulness of this PET scan will be evaluated to determine whether radiation may be left out in the treatment of disease if the PET scan shows that the patient has responded to chemotherapy alone. The plan is to identify a group of patients using early PET scans in order to change to a chemotherapy treatment called BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone). It is one of the most highly effective chemotherapy regimens for Hodgkin lymphoma, but is associated with more side effects than ABVD. Although it has become standard of care in Europe, its use has been more limited in the U.S. because of concerns about toxicity.

Detailed Description

This is single-arm phase II clinical trial of response-adapted therapy based on PET for bulky stage I and stage II Hodgkin lymphoma. A maximum of 123 patients will be entered to the study. The primary outcome of this study is progression-free survival (PFS), defined as the time from study entry to disease progression or death.

Primary Objective:

To determine the progression-free survival (PFS) at 36 months from enrollment for patients with bulky stage I and II Hodgkin lymphoma. All patients will begin treatment with ABVD. Patients who are PET negative after 2 cycles of chemotherapy will receive 6 cycles of ABVD without radiotherapy. Patients who are PET positive after 2 cycles of ABVD will then receive 4 cycles of escalated BEACOPP followed by IFRT. A comparison will be made of the 36-month PFS between patients who are PET positive and those who are PET negative following 2 cycles of ABVD.

Secondary Objectives:

1. To evaluate the complete response (CR) rate of patients diagnosed with bulky stage I and II Hodgkin lymphoma following PET response-adapted chemotherapy with or without radiation therapy.

2. To determine the predictive value of FDG uptake using various semiquantitative approaches, at baseline, after 2 cycles of ABVD and at completion of therapy.

3. To determine the predictive value of volumetric vs. 2 dimensional (2-D) measurement changes on CT between baseline and after 2 cycles, at the end of chemotherapy (PET negative patients only) and after RT (PET positive patients only) and compare with PET parameters.

4. To determine if changes in both qualitative and semiquantitative FDG-PET findings between baseline and after cycle 2, at end of chemotherapy (PET negative patients only) and after RT (PET positive patients only) with combination analyses with incorporating changes obtained from dedicated CT scans, correlate with response and PFS.

5. 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 IPS.

6. To assess whether elevated baseline serum soluble CD30 (sCD30), IL10, CCL17, and CCL22 correlate with clinical response and PFS.

7. To assess whether persistent or recurrent elevation of serial serum sCD30, IL10, CCL17, or CCL22 correlate with relapse/progression or PET scan results.

8. To confirm independently useful tissue biomarkers (bcl-2, MAL, FOXP3, CD68, GzB) for risk stratification in patients with bulky stage I and II Hodgkin lymphoma treated with this regimen.

9. To compare mediastinal bulk on standing PA and lateral chest x-ray (> 0.33 maximum chest diameter) with chest CT (mass > 10 cm).

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 2-3 years, and then once a year for a maximum of ten years from the time of entry on the study.

Conditions

Lymphoma

Keywords

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ABVD +/- BEACOPP + radiation

Patients receive ABVD administered by intravenous (IV) infusion on days 1 and 15 of each cycle. A cycle is considered 28 days. Patients receive a total of two cycles.

Patients undergo a PET scan following two cycles of ABVD. If the PET scan is negative, then the patient will receive four more cycles of ABVD (a total of 6 cycles of ABVD). If the PET scan is positive, then the patient receives four cycles of escalated BEACOPP for 21 days (a total of 4 cycles).

3-6 weeks after BEACOPP therapy, patients receive radiation therapy for 5 days per week (a total of 3.5 weeks).

All patients will be followed for a maximum of ten years.

Group Type: EXPERIMENTAL

ABVD

Intervention Type: DRUG

doxorubicin 25 mg/m\^2 IV bleomycin 10 units/m\^2 IV vinblastine 6 mg/m\^2 IV dacarbazine 375 mg/m\^2 IV

BEACOPP

Intervention Type: DRUG

bleomycin 10 units/m\^2 IV on Day 8 etoposide 200 mg/m\^2 IV on Days 1, 2 and 3 doxorubicin 35 mg/m\^2 IV on Day 1 cyclophosphamide 1250 mg/m\^2 IV on Day 1 vincristine 1.4 mg/m\^2 IV on Day 8 procarbazine 100 mg/m\^2 orally on Days 1-7 prednisone 40 mg/m\^2 orally on Days 1-14

radiation therapy

Intervention Type: RADIATION

Interventions

ABVD

doxorubicin 25 mg/m\^2 IV bleomycin 10 units/m\^2 IV vinblastine 6 mg/m\^2 IV dacarbazine 375 mg/m\^2 IV

Intervention Type: DRUG

BEACOPP

bleomycin 10 units/m\^2 IV on Day 8 etoposide 200 mg/m\^2 IV on Days 1, 2 and 3 doxorubicin 35 mg/m\^2 IV on Day 1 cyclophosphamide 1250 mg/m\^2 IV on Day 1 vincristine 1.4 mg/m\^2 IV on Day 8 procarbazine 100 mg/m\^2 orally on Days 1-7 prednisone 40 mg/m\^2 orally on Days 1-14

Intervention Type: DRUG

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Nodular lymphocyte predominant Hodgkin lymphoma is excluded.
• Core needle biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping. Fine needle aspirates are not acceptable. If multiple specimens are available, please submit the most recent. Failure to submit pathology materials within 60 days of patient registration will be considered a major protocol violation.
• Patients must have a mediastinal mass > 0.33 maximum intrathoracic diameter on standing postero-anterior chest x-ray or mass measuring > 10 cm in its largest diameter.

2. Second Malignancy: No "currently active" second malignancy other than non-melanoma 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 less than 30% risk of relapse.

3. Prior Therapy - Patients may have had one cycle only of ABVD prior to enrolling on study. No other prior treatment (chemotherapy or radiation therapy) for Hodgkin lymphoma is allowed. If patient has had one cycle of ABVD, in order to be eligible to enroll on CALGB 50801, the patient must have had all of the following tests prior to starting the first cycle of ABVD:

• LVEF by ECHO or MUGA
• PFTs (including DLCO/FVC)CT scan (neck*, chest, abdomen, pelvis)
• FDG-PET/CT scan
• Chest X-ray, PA & Lateral
• CBC, differential, platelets
• ESR
• Serum creatinine
• Glucose
• AST
• Alkaline phosphatase
• Bilirubin
• LDH

Patients with a negative FDG-PET/CT scan do not need to have had a dedicated neck CT scan prior to starting the previous cycle of ABVD.

4. ECOG Performance status 0-2.

5. LVEF and DLCO - LVEF by ECHO or MUGA within institutional normal limits unless thought to be disease related. DLCO ≥ 60% with no symptomatic pulmonary disease unless thought to be disease related.

6. HIV Infection - Patients with known HIV must have a CD4 count > 350 and be on concurrent antiretrovirals. Patients with a history of intravenous drug abuse or any behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. An HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk.

7. Pregnancy Restrictions - Non-pregnant and non-nursing. Due to the teratogenic potential of the agents used in this study, pregnant or nursing women may not be enrolled. Women and men of reproductive potential should agree to use an effective means of birth control.

8. Age Restricitions - Age 18 - 60 years

9. Initial Required Laboratory Data:

• ANC ≥ 1000/μL
• Platelet count ≥ 100,000/μL
• Serum Creatinine ≤ 2 mg/dL
• Bilirubin* ≤ 2 x upper limit of normal
• AST ≤ 2 x upper limit of normal* - In the absence of Gilbert's disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ann S. LaCasce, MD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

Naval Medical Center -San Diego

San Diego, California, United States

Saint Helena Hospital

St. Helena, California, United States

Beebe Medical Center

Lewes, Delaware, United States

Delaware Clinical and Laboratory Physicians PA

Newark, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Weiss Memorial Hospital

Chicago, Illinois, United States

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Memorial Regional Cancer Center Day Road

Mishawaka, Indiana, United States

Memorial Hospital of South Bend

South Bend, Indiana, United States

Cancer Center of Kansas - Wichita

Wichita, Kansas, United States

Via Christi Regional Medical Center

Wichita, Kansas, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Union Hospital of Cecil County

Elkton, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Saint John's Hospital - Healtheast

Maplewood, Minnesota, United States

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, United States

Regions Hospital

Saint Paul, Minnesota, United States

Saint Francis Regional Medical Center

Shakopee, Minnesota, United States

Mercy Hospital Springfield

Springfield, Missouri, United States

CoxHealth South Hospital

Springfield, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Norris Cotton Cancer Center-Nashua

Nashua, New Hampshire, United States

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Weill Medical College of Cornell University

New York, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

State University of New York Upstate Medical University

Syracuse, New York, United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Carolinas HealthCare System NorthEast

Concord, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Wayne Memorial Hospital

Goldsboro, North Carolina, United States

Iredell Memorial Hospital

Statesville, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Toledo Clinic Cancer Centers-Maumee

Maumee, Ohio, United States

Saint Charles Hospital

Oregon, Ohio, United States

Flower Hospital

Sylvania, Ohio, United States

Mercy Saint Anne Hospital

Toledo, Ohio, United States

Toledo Clinic Cancer Centers-Toledo

Toledo, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Geisinger Medical Oncology-Lewisburg

Lewisburg, Pennsylvania, United States

Geisinger Wyoming Valley/Henry Cancer Center

Wilkes-Barre, Pennsylvania, United States

Saint Francis Hospital

Greenville, South Carolina, United States

Saint Francis Cancer Center

Greenville, South Carolina, United States

Spartanburg Medical Center

Spartanburg, South Carolina, United States

Central Vermont Medical Center/National Life Cancer Treatment

Berlin Corners, Vermont, United States

University of Vermont College of Medicine

Burlington, Vermont, United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States

Countries

United States

References

Kreuzberger N, Goldkuhle M, von Tresckow B, Kobe C, Sickinger MT, Monsef I, Skoetz N. Positron emission tomography-adapted therapy for first-line treatment in adults with Hodgkin lymphoma. Cochrane Database Syst Rev. 2025 Mar 26;3(3):CD010533. doi: 10.1002/14651858.CD010533.pub3.

Reference Type: DERIVED

PMID: 40135712 (View on PubMed)

LaCasce AS, Dockter T, Ruppert AS, Kostakoglu L, Schoder H, Hsi E, Bogart J, Cheson B, Wagner-Johnston N, Abramson J, Blum K, Leonard JP, Bartlett NL. Positron Emission Tomography-Adapted Therapy in Bulky Stage I/II Classic Hodgkin Lymphoma: CALGB 50801 (Alliance). J Clin Oncol. 2023 Feb 10;41(5):1023-1034. doi: 10.1200/JCO.22.00947. Epub 2022 Oct 21.

Reference Type: DERIVED

PMID: 36269899 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.cancer.gov/about-cancer/treatment/clinical-trials/search/v?id=NCI-2011-02034&q=CALGB-50801

Clinical trial summary from the National Cancer Institute's PDQ® database

Other Identifiers

CDR0000669076

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2011-02034

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-50801

Identifier Type: -

Identifier Source: org_study_id