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

NCT ID: NCT00678327

Last Updated: 2024-05-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1202 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-08-29

Study Completion Date

2024-05-01

Brief Summary

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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

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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.

Conditions

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Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

bleomycin sulfate

Intervention Type BIOLOGICAL

Given IV

dacarbazine

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

vinblastine sulfate

Intervention Type DRUG

Given IV

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.

Group Type ACTIVE_COMPARATOR

dacarbazine

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

vinblastine sulfate

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

bleomycin sulfate

Intervention Type BIOLOGICAL

Given IV

filgrastim

Intervention Type BIOLOGICAL

Given subcutaneously

pegfilgrastim

Intervention Type BIOLOGICAL

Given subcutaneously

cyclophosphamide

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

etoposide

Intervention Type DRUG

Given IV

prednisolone

Intervention Type DRUG

Given orally

procarbazine hydrochloride

Intervention Type DRUG

Given orally

vincristine sulfate

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

bleomycin sulfate

Intervention Type BIOLOGICAL

Given IV

filgrastim

Intervention Type BIOLOGICAL

Given subcutaneously

pegfilgrastim

Intervention Type BIOLOGICAL

Given subcutaneously

cyclophosphamide

Intervention Type DRUG

Given IV

doxorubicin hydrochloride

Intervention Type DRUG

Given IV

etoposide

Intervention Type DRUG

Given IV

prednisolone

Intervention Type DRUG

Given orally

procarbazine hydrochloride

Intervention Type DRUG

Given orally

vincristine sulfate

Intervention Type DRUG

Given IV

Interventions

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bleomycin sulfate

Given IV

Intervention Type BIOLOGICAL

filgrastim

Given subcutaneously

Intervention Type BIOLOGICAL

pegfilgrastim

Given subcutaneously

Intervention Type BIOLOGICAL

cyclophosphamide

Given IV

Intervention Type DRUG

dacarbazine

Given IV

Intervention Type DRUG

doxorubicin hydrochloride

Given IV

Intervention Type DRUG

etoposide

Given IV

Intervention Type DRUG

prednisolone

Given orally

Intervention Type DRUG

procarbazine hydrochloride

Given orally

Intervention Type DRUG

vinblastine sulfate

Given IV

Intervention Type DRUG

vincristine sulfate

Given IV

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research UK

OTHER

Sponsor Role collaborator

Cancer Research UK & UCL Cancer Trials Centre

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Peter Johnson, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Southampton NHS Foundation Trust

Locations

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Southampton General Hospital

Southampton, England, United Kingdom

Site Status

Countries

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United Kingdom

References

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Kreuzberger N, Goldkuhle M, von Tresckow B, Kobe C, Sickinger MT, Monsef I, Skoetz N. Positron emission tomography-adapted therapy for first-line treatment in adults with Hodgkin lymphoma. Cochrane Database Syst Rev. 2025 Mar 26;3(3):CD010533. doi: 10.1002/14651858.CD010533.pub3.

Reference Type DERIVED
PMID: 40135712 (View on PubMed)

Luminari S, Fossa A, Trotman J, Molin D, d'Amore F, Enblad G, Berkahn L, Barrington SF, Radford J, Federico M, Kirkwood AA, Johnson PWM. Long-Term Follow-Up of the Response-Adjusted Therapy for Advanced Hodgkin Lymphoma Trial. J Clin Oncol. 2024 Jan 1;42(1):13-18. doi: 10.1200/JCO.23.01177. Epub 2023 Oct 26.

Reference Type DERIVED
PMID: 37883739 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30220622 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27332902 (View on PubMed)

Other Identifiers

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CRUK-2007-006064-30

Identifier Type: -

Identifier Source: secondary_id

CRUK-07/146

Identifier Type: -

Identifier Source: secondary_id

CDR0000593562

Identifier Type: -

Identifier Source: org_study_id

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