Response-Based Therapy Assessed By PET Scan in Treating Patients With Bulky Stage I and Stage II Classical Hodgkin Lymphoma
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.
|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)|
- Progression-free survival at 36 months from enrollment [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
- 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 ]
|Study Start Date:||September 2010|
|Estimated Primary Completion Date:||July 2017 (Final data collection date for primary outcome measure)|
Experimental: 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.
doxorubicin 25 mg/m^2 IV bleomycin 10 units/m^2 IV vinblastine 6 mg/m^2 IV dacarbazine 375 mg/m^2 IVDrug: 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 1-14Radiation: radiation therapy
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.
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.
- 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.
- To determine the predictive value of FDG uptake using various semiquantitative approaches, at baseline, after 2 cycles of ABVD and at completion of therapy.
- 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.
- 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.
- 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.
- 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, CD68, GzB) for risk stratification in patients with bulky stage I and II Hodgkin lymphoma treated with this regimen.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01118026
|Contact: Ann S. LaCasce, MD||617 632-5959|
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|Study Chair:||Ann S. LaCasce, MD||Dana-Farber Cancer Institute|