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LymphomaPhase 3NCT00433459

Combination Chemotherapy in Treating Young Patients With Hodgkin's Lymphoma

A Phase 3 study testing cyclophosphamide, dacarbazine and prednisolone in people with Lymphoma, run by Christine Mauz-Körholz at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Read more about this study

Who is it for?
Ages Up to 17 years
Conditions the study is for
Lymphoma
What is being tested?
cyclophosphamide, dacarbazine and prednisolone
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2,134 participants
Where
2 sitesin 2 countries
Study dates
Jan 2007to Jan 2013
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 17 years
  • All sexes
  • No healthy volunteers
  • Child

DISEASE CHARACTERISTICS:

  • Histologically confirmed classical Hodgkin's lymphoma
  • No lymphocyte-predominant Hodgkin's lymphoma
  • Fine-needle biopsy not sufficient
  • No prior treatment for Hodgkin's lymphoma except for recommended pre-phase therapy for a large mediastinal tumor

PATIENT CHARACTERISTICS:

  • No known hypersensitivity or contraindication to study drugs
  • No other current malignancy
  • No severe concurrent disease (e.g., immune deficiency syndrome)
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for up to 1 year after completion of study treatment
  • No known HIV positivity

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior chemotherapy or radiotherapy
  • At least 30 days since prior and no other concurrent investigational drugs or participation in another investigational trial

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Germany1 site

  • Universitaetsklinikum Giessen-Marburg

    Giessen, D-35385

Other trials in Germany

United Kingdom1 site

  • Royal Hospital for Sick Children

    Edinburgh, Scotland, EH9 1LF

Other trials in United Kingdom

About this study

Official title: First International Inter-Group Study for Classical Hodgkin's Lymphoma in Children and Adolescents

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to compare how well they work in treating young patients with Hodgkin's lymphoma.

Read the detailed description

OBJECTIVES:

Primary

  • Determine whether the 5-year event-free survival (EFS) rate in pediatric patients with Hodgkin's lymphoma with an adequate response after 2 courses of vincristine, etoposide, prednisone, and doxorubicin hydrochloride (OEPA) (without radiotherapy) are consistent with an estimated target EFS rate of 90%.
  • Compare the EFS (without a deterioration) of patients treated with procarbazine hydrochloride vs dacarbazine (treatment groups 2 and 3).
  • Determine the treatment outcome of a standardized risk-adapted relapse strategy in these patients.

Secondary

  • Determine whether the 5-year EFS rate in patients with Hodgkin's lymphoma with an inadequate response after 2 OEPA courses and standard involved-field radiotherapy are consistent with an estimated target EFS rate of 90%.
  • Determine whether a positive positron emission tomography scan before planned high-dose chemotherapy with autologous stem cell transplantation has a negative prognostic significance.
  • Compare the effect of dacarbazine vs procarbazine on the rate of infertility in males and premature menopause in females (treatment groups 2 and 3).

Tertiary

  • Determine the impact of real-time central staging and response assessment on treatment outcome in these patients.

OUTLINE: This is a randomized, controlled, parallel-group, open-label, multicenter study. Patients are stratified according to staging and response assessment (central vs local) and disease stage (IA/B or IIA [first-line treatment group 1] vs I_EA/B, II_EA, IIB, or IIIA [first-line treatment group 2] vs II_EB, III_E A/B, IIIB, or IVA/B [first-line treatment group 3]).

  • First-line treatment group 1: Patients receive oral prednisone (or prednisolone) 3 times daily on days 1-15, vincristine IV on days 1, 8, and 15, doxorubicin hydrochloride IV over 1-6 hours on days 1 and 15, and etoposide (or etoposide phosphate) IV over 1-2 hours on days 1-5 (OEPA).

Treatment repeats every 28 days for 2 courses in the absence of unacceptable toxicity. Patients are assessed by fludeoxyglucose F 18 positron emission tomography (^18FDG-PET) scan. Patients with inadequate response undergo radiotherapy within 35 days after completion of OEPA.

  • First-line treatment group 2: Patients receive OEPA as in group 1. After completion of OEPA, patients are randomized to 1 of 2 treatment arms.
  • Arm I: Patients receive oral prednisone (or prednisolone) 3 times daily and oral procarbazine hydrochloride 2-3 times a day on days 1-15 and vincristine IV and cyclophosphamide IV over 1 hour on days 1 and 8 (COPP).
  • Arm II: Patients receive oral prednisone (or prednisolone) 3 times daily on days 1-15, dacarbazine IV over 15-30 minutes on days 1-3, and vincristine IV and cyclophosphamide IV over 1 hour on days 1 and 8 (COPDAC).

In both arms, treatment repeats every 28 days for 2 courses in the absence of unacceptable toxicity. Patients are assessed by ^18FDG-PET scan. Patients with an inadequate response undergo radiotherapy within 35 days after completion of COPP or COPDAC.

  • First-line treatment group 3: Patients receive OEPA as in group 1. After completion of OEPA, patients are randomized to 1 of 2 treatment arms.
  • Arm I: Patients receive COPP as in arm I of group 2.
  • Arm II: Patients receive COPDAC as in arm II of group 2. In both arms, treatment repeats every 28 days for 4 courses in the absence of unacceptable toxicity. Patients are assessed by ^18FDG-PET scan. Patients with an inadequate response undergo radiotherapy within 35 days after completion of COPP or COPDAC.

Patients with biopsy-confirmed disease progression OR relapse after first-line treatment on this study or on protocols DAL-HD 90, GPOH-HD 95, GPOHHD 2002 Pilot, or similar treatment proceed to second-line therapy. Patients are stratified according to relapse/progression status (late relapse from first-line treatment group 1 [second-line treatment group 1] vs early relapse from first-line treatment groups 1, 2, or 3 or late relapse from first-line treatment groups 2 or 3 [second-line treatment group 2] vs disease progression [second-line treatment group 3]). Patients undergo a ^18FDG-PET scan prior to beginning second-line therapy.

  • Second-line treatment group 1: Patients receive ifosfamide IV over 22 hours and etoposide IV over 1-2 hours and oral prednisone three times daily on days 1-5 (IEP). Patients then receive doxorubicin hydrochloride IV over 1-6 hours, bleomycin IV, vinblastine IV, and dacarbazine IV over 15-30 minutes on days 22 and 36 (ABVD). Treatment repeats every 50 days for 2 courses in the absence of disease progression or unacceptable toxicity.

After chemotherapy treatment, patients undergo radiotherapy.

  • Second-line treatment group 2: Patients receive IEP and ABVD as in group 1. Autologous stem cells are collected after course 1 or 2 of IEP/ABVD.

After chemotherapy, patients with an adequate response undergo radiotherapy. Patients with an inadequate response undergo high-dose chemotherapy comprising carmustine IV over 1-2 hours on day -7, etoposide IV and cytarabine IV over 30 minutes twice daily on days -6 to -3, and melphalan IV over 1½ hours on day -2. Patients then undergo autologous hematopoietic stem cell transplantation (HSCT).

Patients undergo a ^18FDG-PET scan on day 50-54. Patients with ^18FDG-PET scan positive disease undergo radiotherapy.

  • Second-line treatment group 3: Patients receive IEP and ABVD as in group 1. All patients then undergo high-dose chemotherapy and HSCT as in group 2.

Patients undergo a ^18FDG-PET scan on day 50-54. Patients with ^18FDG-PET scan positive disease undergo radiotherapy.

After completion of study therapy, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 2,150 patients will be accrued for this study.

Conditions
Lymphoma
Being tested
cyclophosphamide, dacarbazine, prednisolone, prednisone, procarbazine hydrochloride
Keywords
childhood lymphocyte depletion Hodgkin lymphoma, childhood mixed cellularity Hodgkin lymphoma, childhood nodular sclerosis Hodgkin lymphoma, stage I childhood Hodgkin lymphoma, stage II childhood Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma
Medical subject headings
Lymphoma, Hodgkin Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cyclophosphamideDrug

    Also called CYC

    drug is used in first line treatment in combination (COPP or COPDAC)

  • dacarbazineDrug

    Also called DTIC

    drug is used in first line treatment in combination (COPDAC)

  • prednisoloneDrug

    drug is used in first line treatment in combination (OEPA, COPP or COPDAC)

  • prednisoneDrug

    drug is used in first line treatment in combination (OEPA, COPP or COPDAC)

  • procarbazine hydrochlorideDrug

    drug is used in first line treatment in combination (COPP)

  • vincristine sulfateDrug

    Also called VCR

    drug is used in first line treatment in combination (OEPA, COPP or COPDAC)

  • fludeoxyglucose F 18Radiation

    used as a diagnostic marker for metabolically active tumour at staging and response assessment

  • radiation therapyRadiation

    Also called IFRT

    part of combination treatment (combined modality between chemo- and radiotherapy)

Study groups in NCT00433459
Study groupRoleWhat they receive
COPPActive comparatorprocarbazine-containing consolidation chemotherapy arm
Receives: Drug: cyclophosphamide; Drug: prednisolone; Drug: prednisone; Drug: procarbazine hydrochloride; Drug: vincristine sulfate; Radiation: fludeoxyglucose F 18; Radiation: radiation therapy
COPDACExperimentalprocarbazine-free consolidation chemotherapy arm
Receives: Drug: cyclophosphamide; Drug: dacarbazine; Drug: prednisolone; Drug: prednisone; Drug: vincristine sulfate; Radiation: fludeoxyglucose F 18; Radiation: radiation therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free survival

    Measured: 5 years

Secondary outcomes (6)

  1. Overall survival

    Measured: 5 years

  2. Progression-free survival

    Measured: 5 years

  3. CTC (Common toxicity criteria) toxicity levels of therapy elements

    Measured: 5 years

  4. Evidence of male infertility score

    Measured: 5 years

  5. Evidence of female infertility score

    Measured: 5 years

  6. Long-term consequences (e.g., premature menopause, secondary cancer)

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2007 (estimated)
  2. Study startJan 2007
  3. Primary completionJan 2013
  4. Study completionJan 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
2,134 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00433459
Sponsor's protocol ID
CDR0000531687
Other IDs
EURONET-PHL-C1, EU-20703, EUDRACT-2006-000995-33, CCLG-HD-2007-10
Status last verified
Mar 2020
First submitted
8 Feb 2007
Last updated
26 Mar 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Kurch L, Landman-Parker J, Georgi TW, Attarbaschi A, Balwierz W, Beishuizen A, Braun M, Cepelova M, Ceppi F, Claviez A, Daw S, Dieckmann K, Fernandez-Teijeiro A, Flerlage JE, Fossa A, Hjalgrim LL, Hraskova A, Karlen J, Klekawka T, Leblanc T, Montravers F, Lopci E, Mascarin M, Pears J, Pelz T, Prelog T, Rohde M, Sabri O, Steglich J, Stoevesandt D, Uytterbroeck A, Vordermark D, Wallace WH, Korholz D, Mauz-Korholz C, Kluge R, Hasenclever D. Quantitative Deauville Scoring to Uncover Prognostic Information from 18F-FDG PET-Based Response Assessment: Data from the EuroNet-PHL-C1 Trial. J Nucl Med. 2025 Sep 2;66(9):1331-1337. doi: 10.2967/jnumed.125.269603.

    PubMed 40639904

  • Daw S, Claviez A, Kurch L, Stoevesandt D, Attarbaschi A, Balwierz W, Beishuizen A, Cepelova M, Ceppi F, Fernandez-Teijeiro A, Fossa A, Georgi TW, Hjalgrim LL, Hraskova A, Leblanc T, Mascarin M, Pears J, Landman-Parker J, Prelog T, Klapper W, Ramsay A, Kluge R, Dieckmann K, Pelz T, Vordermark D, Korholz D, Hasenclever D, Mauz-Korholz C. Transplant and Nontransplant Salvage Therapy in Pediatric Relapsed or Refractory Hodgkin Lymphoma: The EuroNet-PHL-R1 Phase 3 Nonrandomized Clinical Trial. JAMA Oncol. 2025 Mar 1;11(3):258-267. doi: 10.1001/jamaoncol.2024.5636.

    PubMed 39745682

  • Pabari R, McCarten K, Flerlage J, Lai H, Mauz-Korholz C, Dieckmann K, Palese M, Kaste S, Castellino SM, Kelly KM, Stoevesandt D, Kurch L. Hodgkin lymphoma involving the extra-axial CNS: an AHOD1331, PHL-C1, and PHL-C2 report from the COG and EuroNet-PHL. Blood Adv. 2024 Sep 24;8(18):4856-4865. doi: 10.1182/bloodadvances.2023012346.

    PubMed 39058968

  • Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28.

    PubMed 37505794

  • Mauz-Korholz C, Landman-Parker J, Fernandez-Teijeiro A, Attarbaschi A, Balwierz W, Bartelt JM, Beishuizen A, Boudjemaa S, Cepelova M, Ceppi F, Claviez A, Daw S, Dieckmann K, Fossa A, Gattenlohner S, Georgi T, Hjalgrim LL, Hraskova A, Karlen J, Kurch L, Leblanc T, Mann G, Montravers F, Pears J, Pelz T, Rajic V, Ramsay AD, Stoevesandt D, Uyttebroeck A, Vordermark D, Korholz D, Hasenclever D, Wallace WH, Kluge R. Response-adapted omission of radiotherapy in children and adolescents with early-stage classical Hodgkin lymphoma and an adequate response to vincristine, etoposide, prednisone, and doxorubicin (EuroNet-PHL-C1): a titration study. Lancet Oncol. 2023 Mar;24(3):252-261. doi: 10.1016/S1470-2045(23)00019-0.

    PubMed 36858722

  • Mauz-Korholz C, Landman-Parker J, Balwierz W, Ammann RA, Anderson RA, Attarbaschi A, Bartelt JM, Beishuizen A, Boudjemaa S, Cepelova M, Claviez A, Daw S, Dieckmann K, Fernandez-Teijeiro A, Fossa A, Gattenlohner S, Georgi T, Hjalgrim LL, Hraskova A, Karlen J, Kluge R, Kurch L, Leblanc T, Mann G, Montravers F, Pears J, Pelz T, Rajic V, Ramsay AD, Stoevesandt D, Uyttebroeck A, Vordermark D, Korholz D, Hasenclever D, Wallace WH. Response-adapted omission of radiotherapy and comparison of consolidation chemotherapy in children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma (EuroNet-PHL-C1): a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trial. Lancet Oncol. 2022 Jan;23(1):125-137. doi: 10.1016/S1470-2045(21)00470-8. Epub 2021 Dec 9.

    PubMed 34895479

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing cyclophosphamide, dacarbazine and prednisolone in people with Lymphoma, run by Christine Mauz-Körholz at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival (time frame: 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00433459, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2020.

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