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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00678327
First received: May 9, 2008
Last updated: August 23, 2013
Last verified: June 2009

May 9, 2008
August 23, 2013
August 2008
September 2012   (final data collection date for primary outcome measure)
3-year progression-free survival [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00678327 on ClinicalTrials.gov Archive Site
  • Overall survival [ Designated as safety issue: No ]
  • Acute and chronic toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
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.

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.

Interventional
Phase 3
Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • 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
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1200
Not Provided
September 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Not Provided
United Kingdom
 
NCT00678327
CDR0000593562, CRUK-2007-006064-30, CRUK-07/146
Not Provided
Not Provided
Cancer Research UK
Not Provided
Principal Investigator: Peter Johnson, MD University Hospital Southampton NHS Foundation Trust.
National Cancer Institute (NCI)
June 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP