Combination Chemotherapy in Treating Young Patients With Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Collaborators:
Deutsche Krebshilfe e.V., Bonn (Germany)
Euronet Worldwide
Information provided by (Responsible Party):
Christine Mauz-Körholz, Martin-Luther-Universität Halle-Wittenberg
ClinicalTrials.gov Identifier:
NCT00433459
First received: February 8, 2007
Last updated: November 17, 2015
Last verified: November 2015
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: cyclophosphamide
Drug: dacarbazine
Drug: prednisolone
Drug: prednisone
Drug: procarbazine hydrochloride
Drug: vincristine sulfate
Radiation: fludeoxyglucose F 18
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: First International Inter-Group Study for Classical Hodgkin's Lymphoma in Children and Adolescents

Resource links provided by NLM:


Further study details as provided by Martin-Luther-Universität Halle-Wittenberg:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Progression-free survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Toxicity [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Evidence of male infertility score [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Evidence of female infertility score [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Long-term consequences (e.g., premature menopause, secondary cancer) [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 2134
Study Start Date: January 2007
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: COPP
procarbazine-containing consolidation chemotherapy arm
Drug: cyclophosphamide
drug is used in first line treatment in combination (COPP or COPDAC)
Other Name: 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 Name: 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 Name: IFRT
Experimental: COPDAC
procarbazine-free consolidation chemotherapy arm
Drug: cyclophosphamide
drug is used in first line treatment in combination (COPP or COPDAC)
Other Name: CYC
Drug: dacarbazine
drug is used in first line treatment in combination (COPDAC)
Other Name: DTIC
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 Name: 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 Name: IFRT

  Hide Detailed Description

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.

  Eligibility

Ages Eligible for Study:   up to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433459

Locations
Germany
Universitaetsklinikum Giessen-Marburg
Giessen, Germany, D-35385
United Kingdom
Royal Hospital for Sick Children
Edinburgh, Scotland, United Kingdom, EH9 1LF
Sponsors and Collaborators
Christine Mauz-Körholz
Deutsche Krebshilfe e.V., Bonn (Germany)
Euronet Worldwide
Investigators
Study Chair: Dieter Koerholz, MD Martin-Luther-Universität Halle-Wittenberg
Principal Investigator: W. Hamish Wallace, MD Royal Hospital for Sick Children
Principal Investigator: Judith Landman-Parker, MD Hopital d'Enfants Trousseau
  More Information

Responsible Party: Christine Mauz-Körholz, Prof. Dr. med. Christine Mauz-Körholz, Martin-Luther-Universität Halle-Wittenberg
ClinicalTrials.gov Identifier: NCT00433459     History of Changes
Other Study ID Numbers: CDR0000531687  EURONET-PHL-C1  EU-20703  EUDRACT-2006-000995-33  CCLG-HD-2007-10 
Study First Received: February 8, 2007
Last Updated: November 17, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Martin-Luther-Universität Halle-Wittenberg:
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

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Prednisone
Vincristine
Prednisolone
Procarbazine
Fluorodeoxyglucose F18
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Tubulin Modulators

ClinicalTrials.gov processed this record on July 28, 2016