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

• ClinicalTrials.gov Identifier: NCT00678327
• Recruitment Status: Completed
• First Posted: May 15, 2008
• Last Update Posted: May 8, 2024
• Sponsor: University College, London
• Collaborators: Cancer Research UK; Cancer Research UK & UCL Cancer Trials Centre
• Information provided by (Responsible Party): University College, London

Tracking Information

• First Submitted Date: May 9, 2008
• First Posted Date: May 15, 2008
• Last Update Posted Date: May 8, 2024
• Actual Study Start Date: August 29, 2008
• Actual Primary Completion Date: January 31, 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 24, 2018): 3-year progression-free survival [ Time Frame: 3 years ]
• Original Primary Outcome Measures (submitted: May 13, 2008): 3-year progression-free survival

Current Secondary Outcome Measures (submitted: January 24, 2018)

• Overall survival [ Time Frame: 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 ]

Original Secondary Outcome Measures (submitted: May 13, 2008)

• Overall survival
• Acute and chronic toxicity as assessed by NCI CTCAE v3.0

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Randomized Phase III Trial to Assess Response Adapted Therapy Using FDG-PET Imaging in Patients With Newly Diagnosed, Advanced Hodgkin Lymphoma

Brief Summary

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.

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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma

Intervention

• Biological: bleomycin sulfate
  Given IV
• Biological: filgrastim
  Given subcutaneously
• Biological: pegfilgrastim
  Given subcutaneously
• Drug: cyclophosphamide
  Given IV
• Drug: dacarbazine
  Given IV
• Drug: doxorubicin hydrochloride
  Given IV
• Drug: etoposide
  Given IV
• Drug: prednisolone
  Given orally
• Drug: procarbazine hydrochloride
  Given orally
• Drug: vinblastine sulfate
  Given IV
• Drug: vincristine sulfate
  Given IV

Study Arms

• 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.
  Interventions:

  • Biological: bleomycin sulfate
  • Drug: dacarbazine
  • Drug: doxorubicin hydrochloride
  • Drug: vinblastine sulfate
• 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.
  Interventions:

  • Drug: dacarbazine
  • Drug: doxorubicin hydrochloride
  • Drug: vinblastine sulfate
• 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.
  Interventions:

  • Biological: bleomycin sulfate
  • Biological: filgrastim
  • Biological: pegfilgrastim
  • Drug: cyclophosphamide
  • Drug: doxorubicin hydrochloride
  • Drug: etoposide
  • Drug: prednisolone
  • Drug: procarbazine hydrochloride
  • Drug: vincristine sulfate
• 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.
  Interventions:

  • Biological: bleomycin sulfate
  • Biological: filgrastim
  • Biological: pegfilgrastim
  • Drug: cyclophosphamide
  • Drug: doxorubicin hydrochloride
  • Drug: etoposide
  • Drug: prednisolone
  • Drug: procarbazine hydrochloride
  • Drug: vincristine sulfate

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 24, 2018): 1202
• Original Enrollment (submitted: May 13, 2008): 1200
• Actual Study Completion Date: May 1, 2024
• Actual Primary Completion Date: January 31, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT00678327
• Other Study ID Numbers: CDR0000593562; CRUK-2007-006064-30; CRUK-07/146
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University College, London
• Original Responsible Party: Not Provided
• Current Study Sponsor: University College, London
• Original Study Sponsor: Cancer Research UK

Collaborators

• Cancer Research UK
• Cancer Research UK & UCL Cancer Trials Centre

Investigators

• Principal Investigator: Peter Johnson, MD; University Hospital Southampton NHS Foundation Trust

• PRS Account: University College, London
• Verification Date: May 2024