Combination Chemotherapy in Treating Young Patients With Hodgkin's Lymphoma

March 24, 2020 updated by: Christine Mauz-Körholz

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

2134

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Giessen, Germany, D-35385
        • Universitaetsklinikum Giessen-Marburg
  • United Kingdom
    • Scotland
      • Edinburgh, Scotland, United Kingdom, EH9 1LF
        • Royal Hospital for Sick Children

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: COPP
procarbazine-containing consolidation chemotherapy arm
Drug: cyclophosphamide
drug is used in first line treatment in combination (COPP or COPDAC)
Other Names:
  • CYC
Drug: prednisolone
drug is used in first line treatment in combination (OEPA, COPP or COPDAC)
Drug: prednisone
drug is used in first line treatment in combination (OEPA, COPP or COPDAC)
Drug: procarbazine hydrochloride
drug is used in first line treatment in combination (COPP)
Drug: vincristine sulfate
drug is used in first line treatment in combination (OEPA, COPP or COPDAC)
Other Names:
  • VCR
Radiation: fludeoxyglucose F 18
used as a diagnostic marker for metabolically active tumour at staging and response assessment
Radiation: radiation therapy
part of combination treatment (combined modality between chemo- and radiotherapy)
Other Names:
  • IFRT
Experimental: COPDAC
procarbazine-free consolidation chemotherapy arm
Drug: cyclophosphamide
drug is used in first line treatment in combination (COPP or COPDAC)
Other Names:
  • CYC
Drug: prednisolone
drug is used in first line treatment in combination (OEPA, COPP or COPDAC)
Drug: prednisone
drug is used in first line treatment in combination (OEPA, COPP or COPDAC)
Drug: vincristine sulfate
drug is used in first line treatment in combination (OEPA, COPP or COPDAC)
Other Names:
  • VCR
Radiation: fludeoxyglucose F 18
used as a diagnostic marker for metabolically active tumour at staging and response assessment
Radiation: radiation therapy
part of combination treatment (combined modality between chemo- and radiotherapy)
Other Names:
  • IFRT
Drug: dacarbazine
drug is used in first line treatment in combination (COPDAC)
Other Names:
  • DTIC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Event-free survival
Time Frame: 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 5 years
5 years
Progression-free survival
Time Frame: 5 years
5 years
CTC (Common toxicity criteria) toxicity levels of therapy elements
Time Frame: 5 years
5 years
Evidence of male infertility score
Time Frame: 5 years
5 years
Evidence of female infertility score
Time Frame: 5 years
5 years
Long-term consequences (e.g., premature menopause, secondary cancer)
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Christine Mauz-Körholz

Collaborators

Deutsche Krebshilfe e.V., Bonn (Germany)
Euronet Worldwide

Investigators

  • Principal Investigator: W. Hamish Wallace, MD, Royal Hospital for Sick Children
  • Principal Investigator: Judith Landman-Parker, MD, Hopital d'Enfants Trousseau

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

February 8, 2007

First Submitted That Met QC Criteria

February 8, 2007

First Posted (Estimate)

February 12, 2007

Study Record Updates

Last Update Posted (Actual)

March 26, 2020

Last Update Submitted That Met QC Criteria

March 24, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000531687
  • EURONET-PHL-C1
  • EU-20703
  • EUDRACT-2006-000995-33
  • CCLG-HD-2007-10

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma

Clinical Trials on cyclophosphamide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bahrain

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe