Clinical trial NCT01118026: Response-Based Therapy Assessed By PET Scan in Treating Patients With Bulky Stage I and Stage II Classical Hodgkin Lymphoma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2010-05-06
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 1. Documentation of Disease:

   * Histologically documented Hodgkin lymphoma subclassified according to the WHO modification of the Rye Classification and staged according to the modified Ann Arbor Staging Classification system.

     * Patients must have clinical stage IA, IB, IIA or IIB.
     * Patients with "E" extensions will be eligible if all other criteria have been met.
     * 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

Primary outcomes:
measure: Progression-free Survival at 36 Months
timeFrame: Up to 36 months
Secondary outcomes:
measure: Complete Response
timeFrame: Up to 8 weeks
Other outcomes:
measure: 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
timeFrame: Up to 3 years
measure: 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
timeFrame: Up to 3 years
measure: 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 ...
timeFrame: Up to 3 years
measure: Standard Uptake Values (SUVs) for Target Sites Measured at Baseline, After Course 2, and After Completion of Therapy
timeFrame: Up to 3 years
Locations:
city: Saint Helena
country: United States
facility: Saint Helena Hospital
state: California
city: San Diego
country: United States
facility: Naval Medical Center -San Diego
state: California
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: Delaware Clinical and Laboratory Physicians PA
state: Delaware
city: Newark
country: United States
facility: Christiana Care Health System-Christiana Hospital
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Chicago
country: United States
facility: Weiss Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Mishawaka
country: United States
facility: Memorial Regional Cancer Center Day Road
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Wichita
country: United States
facility: Cancer Center of Kansas - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Elkton
country: United States
facility: Union Hospital of Cecil County
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Maplewood
country: United States
facility: Saint John's Hospital - Healtheast
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Saint Louis Park
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Shakopee
country: United States
facility: Saint Francis Regional Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: Mercy Hospital Springfield
state: Missouri
city: Springfield
country: United States
facility: CoxHealth South Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Nashua
country: United States
facility: Norris Cotton Cancer Center-Nashua
state: New Hampshire
city: Camden
country: United States
facility: Cooper Hospital University Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Concord
country: United States
facility: Carolinas HealthCare System NorthEast
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital
state: North Carolina
city: Statesville
country: United States
facility: Iredell Memorial Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Maumee
country: United States
facility: Toledo Clinic Cancer Centers-Maumee
state: Ohio
city: Oregon
country: United States
facility: Saint Charles Hospital
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital
state: Ohio
city: Toledo
country: United States
facility: Mercy Saint Anne Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Centers-Toledo
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Lewisburg
country: United States
facility: Geisinger Medical Oncology-Lewisburg
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley/Henry Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Saint Francis Hospital
state: South Carolina
city: Greenville
country: United States
facility: Saint Francis Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Berlin
country: United States
facility: Central Vermont Medical Center/National Life Cancer Treatment
state: Vermont
city: Burlington
country: United States
facility: University of Vermont College of Medicine
state: Vermont
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Ann S. LaCasce, MD
role: STUDY_CHAIR
References:
citation: 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.