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


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Lymphoma

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Trial Information

A Randomized Phase III Trial to Assess Response Adapted Therapy Using FDG-PET Imaging in Patients With Newly Diagnosed, Advanced 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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

3-year progression-free survival

Safety Issue:

No

Principal Investigator

Peter Johnson, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospital Southampton NHS Foundation Trust.

Authority:

Unspecified

Study ID:

CDR0000593562

NCT ID:

NCT00678327

Start Date:

August 2008

Completion Date:

Related Keywords:

  • Lymphoma
  • stage III adult Hodgkin lymphoma
  • stage IV adult Hodgkin lymphoma
  • adult nodular sclerosis Hodgkin lymphoma
  • adult lymphocyte depletion Hodgkin lymphoma
  • adult lymphocyte predominant Hodgkin lymphoma
  • adult mixed cellularity Hodgkin lymphoma
  • stage II adult Hodgkin lymphoma
  • Hodgkin Disease
  • Lymphoma

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