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

NCT00678327 | Completed Phase 3 DMC

• 3 other identifiers: CDR0000593562CRUK-2007-006064-30CRUK-07/146
• Study Type: interventional
• Target: 1,202
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 3-year progression-free survival

  3 years

Secondary Outcomes (2)

• Overall survival

  5 years after last patient recruited

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

  5 years after last patient recruited

Study Arms (4)

Arm I

ACTIVE COMPARATOR

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.

Biological: bleomycin sulfate; Drug: dacarbazine; Drug: doxorubicin hydrochloride; Drug: vinblastine sulfate

Arm II

ACTIVE COMPARATOR

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.

Drug: dacarbazine; Drug: doxorubicin hydrochloride; Drug: vinblastine sulfate

BEACOPP-14 chemotherapy

EXPERIMENTAL

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.

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

BEACOPP-escalated chemotherapy

EXPERIMENTAL

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.

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

Interventions

bleomycin sulfate BIOLOGICAL

Given IV

Arm I; BEACOPP-14 chemotherapy; BEACOPP-escalated chemotherapy

filgrastim BIOLOGICAL

Given subcutaneously

BEACOPP-14 chemotherapy; BEACOPP-escalated chemotherapy

pegfilgrastim BIOLOGICAL

Given subcutaneously

BEACOPP-14 chemotherapy; BEACOPP-escalated chemotherapy

cyclophosphamide DRUG

Given IV

BEACOPP-14 chemotherapy; BEACOPP-escalated chemotherapy

dacarbazine DRUG

Given IV

Arm I; Arm II

doxorubicin hydrochloride DRUG

Given IV

Arm I; Arm II; BEACOPP-14 chemotherapy; BEACOPP-escalated chemotherapy

etoposide DRUG

Given IV

BEACOPP-14 chemotherapy; BEACOPP-escalated chemotherapy

prednisolone DRUG

Given orally

BEACOPP-14 chemotherapy; BEACOPP-escalated chemotherapy

procarbazine hydrochloride DRUG

Given orally

BEACOPP-14 chemotherapy; BEACOPP-escalated chemotherapy

vinblastine sulfate DRUG

Given IV

Arm I; Arm II

vincristine sulfate DRUG

Given IV

BEACOPP-14 chemotherapy; BEACOPP-escalated chemotherapy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University College, London: lead
• Cancer Research UK: collaborator
• Cancer Research UK & UCL Cancer Trials Centre: collaborator

Study Sites (1)

Southampton General Hospital

Southampton, England, SO16 6YD, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 40135712 DERIVED

• 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.

  PMID: 37883739 DERIVED

• 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.

  PMID: 30220622 DERIVED

• 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.

  PMID: 27332902 DERIVED

MeSH Terms

Conditions

Lymphoma; Hodgkin Disease

Interventions

Bleomycin; Filgrastim; pegfilgrastim; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Prednisolone; Procarbazine; Vinblastine; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Peter Johnson, MD

  University Hospital Southampton NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2008
• First Posted: May 15, 2008
• Study Start: August 29, 2008
• Primary Completion: January 31, 2016
• Study Completion: May 1, 2024
• Last Updated: May 8, 2024

Record last verified: 2024-05

Locations

GB (1)