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

Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01118026
• Other study ID #: CALGB-50801
• Secondary ID: CDR0000669076NCI
• Status: Completed
• Phase: Phase 2
• Start date: September 2010
• Est. completion date: September 29, 2021

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: September 29, 2021
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma

Intervention

Drug:
• 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
• 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

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	University of Vermont College of Medicine	Burlington	Vermont
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Weiss Memorial Hospital	Chicago	Illinois
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Carolinas HealthCare System NorthEast	Concord	North Carolina
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Duke University Medical Center	Durham	North Carolina
United States	Union Hospital of Cecil County	Elkton	Maryland
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio
United States	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana
United States	Norris Cotton Cancer Center-Nashua	Nashua	New Hampshire
United States	Weill Medical College of Cornell University	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Saint Charles Hospital	Oregon	Ohio
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Saint Helena Hospital	Saint Helena	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	Naval Medical Center -San Diego	San Diego	California
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Flower Hospital	Sylvania	Ohio
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Mercy Saint Anne Hospital	Toledo	Ohio
United States	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

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
Other	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		Up to 3 years
Other	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		Up to 3 years
Other	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 ...		Up to 3 years
Other	Standard Uptake Values (SUVs) for Target Sites Measured at Baseline, After Course 2, and After Completion of Therapy		Up to 3 years
Primary	Progression-free Survival at 36 Months	Progression-free survival (PFS) is defined as the time from first PET/CT scan to disease progression or death. Patients who are alive without disease progression will be censored at the time of their most recent disease evaluation. The Kaplan-Meier three-year (36 month) survival estimates and confidence intervals are presented below.	Up to 36 months
Secondary	Complete Response	A Complete Response (CR) is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. For this endpoint, the best response at any time post-baseline was analyzed	Up to 8 weeks

External Links

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