Combination Chemotherapy in Treating Young Patients With Hodgkin's Lymphoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2007 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00433459
First received: February 8, 2007
Last updated: June 16, 2011
Last verified: June 2007
  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
Biological: bleomycin sulfate
Drug: carmustine
Drug: cyclophosphamide
Drug: cytarabine
Drug: dacarbazine
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: etoposide phosphate
Drug: ifosfamide
Drug: melphalan
Drug: prednisolone
Drug: prednisone
Drug: procarbazine hydrochloride
Drug: vinblastine sulfate
Drug: vincristine sulfate
Procedure: autologous hematopoietic stem cell transplantation
Radiation: fludeoxyglucose F 18
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
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 National Cancer Institute (NCI):

Primary Outcome Measures:
  • Event-free survival [ Designated as safety issue: No ]

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

Estimated Enrollment: 2150
Study Start Date: January 2007
  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
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 Halle Recruiting
Halle, Germany, D-06097
Contact: Dieter Koerholz, MD    49-345-557-2387      
United Kingdom
Royal Hospital for Sick Children Recruiting
Edinburgh, Scotland, United Kingdom, EH9 1LF
Contact: W. Hamish Wallace, MD    44-131-536-0426      
Sponsors and Collaborators
Martin-Luther-Universität Halle-Wittenberg
Investigators
Study Chair: Dieter Koerholz, MD Martin-Luther-Universität Halle-Wittenberg
Investigator: W. Hamish Wallace, MD Royal Hospital for Sick Children
Investigator: Judith Landman-Parker, MD Hopital d'Enfants Trousseau
  More Information

Additional Information:
No publications provided

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: June 16, 2011
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
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:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bleomycin
Doxorubicin
Etoposide phosphate
Isophosphamide mustard
Carmustine
Cyclophosphamide
Cytarabine
Dacarbazine
Etoposide
Ifosfamide
Melphalan
Prednisolone
Methylprednisolone Hemisuccinate
Prednisone
Procarbazine
Vinblastine
Vincristine
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate

ClinicalTrials.gov processed this record on July 26, 2014