- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00678327
Fludeoxyglucose F 18-PET/CT Imaging in Assessing Response to Chemotherapy in Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Hodgkin Lymphoma
A Randomized Phase III Trial to Assess Response Adapted Therapy Using FDG-PET Imaging in Patients With Newly Diagnosed, Advanced Hodgkin Lymphoma
RATIONALE: Imaging procedures, such as fludeoxyglucose F 18 (FDG)-PET/CT scan, done before, during, and after chemotherapy may help doctors assess a patient's response to treatment and help plan the best treatment. It is not yet known whether FDG-PET/CT imaging is effective in assessing response to chemotherapy in patients with newly diagnosed Hodgkin lymphoma.
PURPOSE: This randomized phase III trial is studying FDG-PET/CT imaging to see how well it works in assessing response to chemotherapy in patients with newly diagnosed stage II, stage III, or stage IV Hodgkin lymphoma.
Study Overview
Status
Conditions
Detailed Description
OBJECTIVES:
- To determine if fludeoxyglucose F 18 (FDG)-PET/CT imaging can be reproducibly and effectively applied in the early assessment of response to chemotherapy in patients with newly diagnosed stage II-IV Hodgkin lymphoma.
- To determine if a negative FDG-PET/CT scan after 2 courses of ABVD chemotherapy comprising doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine can be used to predict a group of patients for whom it is safe to reduce therapy by the subsequent omission of bleomycin, without detriment to progression-free survival.
- To determine if treatment intensification in response to positive FDG-PET/CT imaging after 2 courses of ABVD chemotherapy can improve the outcome by comparison with previous series.
OUTLINE: This is a multicenter study.
Patients undergo fludeoxyglucose F 18 (FDG)-PET/CT imaging at baseline. Patients then receive ABVD chemotherapy comprising doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Between days 22 and 25 of course 2, patients undergo a second FDG-PET/CT scan to assess response. Subsequent therapy is based on FDG-PET/CT scan results.
Negative FDG-PET/CT scan: Patients with a negative FDG-PET/CT scan are randomized to 1 of 2 treatment arms.
- Arm I (ABVD chemotherapy): Patients receive ABVD chemotherapy comprising doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Arm II (AVD chemotherapy): Patients receive AVD chemotherapy comprising doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Positive FDG-PET/CT scan: Patients with a positive FDG-PET/CT scan are assigned to 1 of 2 chemotherapy regimens, as determined by the participating center.
- BEACOPP-14 chemotherapy: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1-3; oral procarbazine hydrochloride and oral prednisolone on days 1-7; and bleomycin IV and vincristine IV on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 8-13 OR pegfilgrastim SC once on day 8. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- BEACOPP-escalated chemotherapy: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1-3; oral procarbazine hydrochloride on days 1-7; oral prednisolone on days 1-14; and bleomycin IV and vincristine IV on day 8. Patients also receive G-CSF SC beginning on day 8 and continuing until blood counts recover OR pegfilgrastim SC once on day 8. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of BEACOPP chemotherapy, patients undergo a third FDG-PET/CT scan to assess response. Patients with a negative FDG-PET/CT scan receive 2 more courses of BEACOPP-14 or 1 more course of BEACOPP-escalated chemotherapy. Patients with a persistently positive FDG-PET/CT scan may receive radiotherapy to sites of FDG uptake or salvage chemotherapy, at the investigator's discretion.
After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
England
-
Southampton, England, United Kingdom, SO16 6YD
- Southampton General Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
DISEASE CHARACTERISTICS:
Histologically confirmed classical Hodgkin lymphoma (HL) meeting the following criteria:
- Meets current WHO classification criteria (i.e., nodular sclerosis, mixed cellularity, lymphocyte rich, and lymphocyte-depleted)
Clinical stage IIB, III, or IV disease OR clinical stage IIA disease with adverse features, including any of the following:
- Bulk mediastinal disease, defined as maximal transverse diameter of mass > 0.33 of the internal thoracic diameter at D5/6 interspace on routine chest x-ray
- Disease outside the mediastinum and lymph node or lymph node mass > 10 cm in diameter
- More than two sites of disease
- Other poor-risk features that require treatment with full course combination chemotherapy
- Newly diagnosed disease
- No CNS or meningeal involvement by lymphoma
PATIENT CHARACTERISTICS:
- ECOG performance status 0-3
- Life expectancy > 3 months
- ANC > 1,500/mm^3 (unless there is bone marrow infiltration by lymphoma)
- Platelet count > 100,000/mm^3 (unless there is bone marrow infiltration by lymphoma)
- Creatinine < 150% of upper limit of normal (ULN)
- Bilirubin < 2.0 times ULN (unless attributed to lymphoma)
- Transaminases < 2.5 times ULN (unless attributed to lymphoma)
- LVEF ≥ 50% (in patients with a significant history of ischemic heart disease or hypertension)
- Diffusion capacity within 25% of normal predicted value by lung function testing
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Amenable to the administration of a full course of chemotherapy, according to the investigator
- Must have access to PET/CT scanning
- No poorly controlled diabetes mellitus
- No cardiac contraindication to doxorubicin hydrochloride, including abnormal contractility by ECHO or MUGA
- No neurological contraindication to chemotherapy (e.g., pre-existing neuropathy)
- No other concurrent uncontrolled medical condition
- No other active malignant disease within the past 10 years, except fully excised basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix
No known positivity for HIV, hepatitis B surface antigen, or hepatitis C
- Routine testing, in the absence of risk factors, is not required
- No medical or psychiatric condition that compromises the patient's ability to give informed consent
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, radiotherapy or other investigational drug for HL
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Arm I
Patients receive ABVD chemotherapy comprising doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV, and dacarbazine IV on days 1 and 15.
Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
|
Given IV
Given IV
Given IV
Given IV
|
Active Comparator: Arm II
Patients receive AVD chemotherapy comprising doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV on days 1 and 15.
Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
|
Given IV
Given IV
Given IV
|
Experimental: BEACOPP-14 chemotherapy
Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1-3; oral procarbazine hydrochloride and oral prednisolone on days 1-7; and bleomycin IV and vincristine IV on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 8-13 OR pegfilgrastim SC once on day 8. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
|
Given IV
Given IV
Given IV
Given IV
Given IV
Given subcutaneously
Given subcutaneously
Given orally
Given orally
|
Experimental: BEACOPP-escalated chemotherapy
Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1-3; oral procarbazine hydrochloride on days 1-7; oral prednisolone on days 1-14; and bleomycin IV and vincristine IV on day 8. Patients also receive G-CSF SC beginning on day 8 and continuing until blood counts recover OR pegfilgrastim SC once on day 8. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
|
Given IV
Given IV
Given IV
Given IV
Given IV
Given subcutaneously
Given subcutaneously
Given orally
Given orally
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
3-year progression-free survival
Time Frame: 3 years
|
3 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall survival
Time Frame: 5 years after last patient recruited
|
5 years after last patient recruited
|
Acute and chronic toxicity as assessed by NCI CTCAE v3.0
Time Frame: 5 years after last patient recruited
|
5 years after last patient recruited
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Peter Johnson, MD, University Hospital Southampton NHS Foundation Trust
Publications and helpful links
General Publications
- Anderson RA, Remedios R, Kirkwood AA, Patrick P, Stevens L, Clifton-Hadley L, Roberts T, Hatton C, Kalakonda N, Milligan DW, McKay P, Rowntree C, Scott FM, Johnson PWM. Determinants of ovarian function after response-adapted therapy in patients with advanced Hodgkin's lymphoma (RATHL): a secondary analysis of a randomised phase 3 trial. Lancet Oncol. 2018 Oct;19(10):1328-1337. doi: 10.1016/S1470-2045(18)30500-X. Epub 2018 Sep 13.
- Johnson P, Federico M, Kirkwood A, Fossa A, Berkahn L, Carella A, d'Amore F, Enblad G, Franceschetto A, Fulham M, Luminari S, O'Doherty M, Patrick P, Roberts T, Sidra G, Stevens L, Smith P, Trotman J, Viney Z, Radford J, Barrington S. Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma. N Engl J Med. 2016 Jun 23;374(25):2419-29. doi: 10.1056/NEJMoa1510093.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Hodgkin Disease
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Prednisolone
- Cyclophosphamide
- Etoposide
- Doxorubicin
- Liposomal doxorubicin
- Vincristine
- Dacarbazine
- Bleomycin
- Vinblastine
- Procarbazine
Other Study ID Numbers
- CDR0000593562
- CRUK-2007-006064-30
- CRUK-07/146
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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