Combination Chemotherapy and Radiation Therapy in Treating Children With Previously Untreated Stage II, Stage III, or Stage IV Hodgkin's Disease

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00004010
First received: November 1, 1999
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. Giving radiation therapy after chemotherapy may be an effective treatment for Hodgkin's disease.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and radiation therapy in treating children who have previously untreated stage II, stage III, or stage IV Hodgkin's disease.


Condition Intervention Phase
Lymphoma
Biological: bleomycin sulfate
Biological: filgrastim
Drug: ABVD regimen
Drug: cyclophosphamide
Drug: dacarbazine
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: prednisone
Drug: procarbazine hydrochloride
Drug: vinblastine sulfate
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study for the Treatment of Children With Newly Diagnosed Advanced Stage Hodgkin's Disease: Upfront Dose Intensive Chemotherapy

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Estimate the rate of BEACOPP )((Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone) specific toxicity in pediatric patients [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Obtain preliminary estimates of response to BEACOPP ((Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone) [ Designated as safety issue: No ]

Enrollment: 99
Study Start Date: October 1999
Study Completion Date: June 2008
Primary Completion Date: October 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BEACOPP therapy

Patients receive 4 cycles of BEACOPP therapy. Drugs utilized in this regimen include Bleomycin (B), Etoposide (E), Doxorubicin (A), Cyclophosphamide (C), Vincristine (O), Prednisone (P) and Procarbazine (P). Each cycle lasts 21 days and is characterized by intravenous pulses of Etoposide (Days 0-2), Doxorubicin (Day 0), Cyclophosphamide (Day 0), Bleomycin (Day 7), Vincristine (Day 7). Seven days of oral procarbazine (Days 0-6) and 14 days of oral prednisone (Days 0-13) are given during each cycle.

Growth factor support with Filgrastim (G-CSF) is given by subcutaneous injection daily beginning Day 8. Response will then be determined and stratification for further treatment.

Biological: bleomycin sulfate
Other Name: Blenoxane
Biological: filgrastim
Other Names:
  • GCSF
  • Neupogen
Drug: ABVD regimen Drug: cyclophosphamide
Other Name: Cytoxan
Drug: dacarbazine Drug: doxorubicin hydrochloride
Other Name: Adriamycin
Drug: etoposide
Other Names:
  • VP-16
  • VePesid
Drug: prednisone Drug: procarbazine hydrochloride
Other Name: Matulane
Drug: vinblastine sulfate
Other Name: Velban
Drug: vincristine sulfate
Other Names:
  • Oncovin
  • Vincasar
  • VCR
  • leurocristine
  • NSC# 67574
Radiation: radiation therapy

Detailed Description:

OBJECTIVES: I. Determine the feasibility and toxicity of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) induction in pediatric patients with previously untreated stage II, stage III, or stage IV Hodgkin's disease. II. Determine rates of complete response and rapid early partial response (defined as greater than 70% reduction in the size of a bulky mediastinal mass or nodal aggregate and a negative gallium scan) in these patients treated with 4 courses of BEACOPP. III. Determine whether thallium scans effectively measure response to therapy in these patients treated with this regimen. IV. Evaluate the expression of markers of apoptosis in tumor samples from these patients at diagnosis and at time of relapse, and correlate expression of these markers with response to therapy and overall outcome. V. Determine the utility of seven molecular genetic markers as surrogate markers of genotoxic damage caused by this regimen in these patients. VI. Estimate the incidence of therapy related late effects, including second malignant neoplasms, sterility, cardiac dysfunction, pulmonary restrictive disease, growth abnormalities, and thyroid disease in these patients.

OUTLINE: Induction: On day 0, patients receive cyclophosphamide IV over 30 minutes, doxorubicin IV over 15-30 minutes, etoposide IV over 1 hour, oral prednisone every 12 hours, and oral procarbazine. On days 1 and 2, patients receive etoposide IV over 1 hour, oral prednisone every 12 hours, and oral procarbazine. On days 3-6, patients receive oral prednisone every 12 hours and oral procarbazine. On day 7, patients receive vincristine IV, bleomycin IV over 5 minutes, and oral prednisone every 12 hours. On days 8-13, patients receive oral prednisone every 12 hours. Beginning on day 8, patients receive filgrastim (G-CSF) subcutaneously until absolute neutrophil counts recover. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Consolidation therapy begins on week 12 or when blood counts recover. Consolidation for rapid early responders (patients with complete response (CR) or rapid early partial response (PR-1) to induction therapy): Females - Patients receive vincristine IV, cyclophosphamide IV over 30 minutes, oral prednisone every 12 hours, and oral procarbazine on day 0. On days 1-6, patients receive oral prednisone every 12 hours and oral procarbazine. On day 7, patients receive vinblastine IV, bleomycin IV over 5 minutes, doxorubicin IV over 15-30 minutes, and oral prednisone every 12 hours. On days 8-13, patients receive oral prednisone every 12 hours. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Males - Patients receive doxorubicin IV over 15-30 minutes, bleomycin IV over 5 minutes, vinblastine IV, and dacarbazine IV on days 0 and 14. Treatment repeats every 28 days for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 3 weeks after completion of chemotherapy, male patients with CR or PR-1 receive radiotherapy 5 days per week to areas of initial disease involvement (total duration of radiotherapy is dependent on initial extent of disease). Consolidation for slow early responders: Patients with slow partial response (PR-2) or stable disease (SD) after 4 courses of induction therapy receive 4 additional courses of induction therapy in the absence of disease progression or unacceptable toxicity. Beginning on day 8, patients receive G-CSF subcutaneously until blood counts recover. Patients should be off G-CSF for more than 24 hours prior to the next course of chemotherapy. Beginning 3 weeks after completion of chemotherapy, male and female patients with PR-2 or SD receive radiotherapy 5 days per week to areas of initial disease involvement (total duration of radiotherapy is dependent on initial extent of disease). Patients are followed every 3 months for 2 years, every 6 months for 1 year, annually for 2 years and then at years 10 and 20.

PROJECTED ACCRUAL: Approximately 25-50 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Histologically proven, previously untreated Hodgkin's disease Stage IV OR Stage II or stage III with B symptoms (at least 1 of the following: unexplained weight loss greater than 10%, unexplained recurrent fever greater than 39 degrees C, or drenching night sweats) AND bulk disease (defined as a mediastinal mass greater than 1/3 of mediastinal thoracic diameter and/or nodal aggregate greater than 10.0 cm) The following cellular types are eligible: Mixed cellularity, not otherwise specified (NOS) Lymphocytic depletion, NOS Lymphocytic depletion, diffuse fibrosis Lymphocytic depletion, reticular Lymphocytic predominance, NOS Lymphocytic predominance, diffuse Lymphocytic predominance, nodular Hodgkin's paragranuloma Hodgkin's granuloma Hodgkin's sarcoma Nodular sclerosis, NOS Nodular sclerosis, cellular phase Nodular sclerosis, lymphocytic predominance Nodular sclerosis, mixed cellularity Nodular sclerosis, lymphocytic depletion Hodgkin's disease, NOS Must begin protocol therapy within 42 days of biopsy and 7 days of completion of staging

PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: No prior treatment for Hodgkin's disease

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00004010

  Show 40 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Kara Kelly, MD Herbert Irving Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Kelly M, Hutchinson R, Sposto R, et al.: BEACOPP chemotherapy is a highly effective regimen in children and adolescents with advanced stage Hodgkin's disease: results from Children's Cancer Group study CCG-59704. [Abstract] Eur J Haematol 75 (Suppl 65): A-WP07, 72, 2004.
Shiramizu B, Morris E, Perkins S, et al.: Identification of patient specific primers (PSPs) of IgH and TCR-y regions by nested PCR in CD20 positive Hodgkin disease: a Children's Cancer Group report (CCG). [Abstract] Ann Oncol 13(suppl 2): A-389, 112, 2002.

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00004010     History of Changes
Other Study ID Numbers: 59704, COG-59704, CDR0000067222
Study First Received: November 1, 1999
Last Updated: February 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Oncology Group:
stage II childhood Hodgkin lymphoma
stage III childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
childhood lymphocyte predominant Hodgkin lymphoma
childhood lymphocyte depletion Hodgkin lymphoma
childhood nodular sclerosis Hodgkin lymphoma
childhood mixed cellularity 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
Liposomal doxorubicin
Etoposide phosphate
Cyclophosphamide
Dacarbazine
Etoposide
Prednisone
Procarbazine
Vinblastine
Vincristine
Lenograstim
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on August 19, 2014