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

February 25, 2014 updated by: Children's Oncology Group

Pilot Study for the Treatment of Children With Newly Diagnosed Advanced Stage Hodgkin's Disease: Upfront Dose Intensive Chemotherapy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

99

Phase

  • Phase 2

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

  • Australia
    • Western Australia
      • Perth, Western Australia, Australia, 6001
        • Princess Margaret Hospital for Children
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6H 3V4
        • British Columbia Children's Hospital
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3J 3G9
        • IWK Health Centre
  • United States
    • California
      • Long Beach, California, United States, 90806
        • Long Beach Memorial Medical Center
      • Los Angeles, California, United States, 90095-1781
        • Jonsson Comprehensive Cancer Center, UCLA
      • Los Angeles, California, United States, 90027-0700
        • Children's Hospital Los Angeles
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • San Francisco, California, United States, 94115-0128
        • UCSF Cancer Center and Cancer Research Institute
      • Travis Air Force Base, California, United States, 94535
        • David Grant Medical Center
    • Colorado
      • Denver, Colorado, United States, 80218
        • Children's Hospital of Denver
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Cancer Research Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5265
        • Indiana University Cancer Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0752
        • University of Michigan Comprehensive Cancer Center
      • Kalamazoo, Michigan, United States, 49007-3731
        • CCOP - Kalamazoo
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Cancer Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68198-3330
        • University of Nebraska Medical Center
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Cancer Institute of New Jersey
      • Paterson, New Jersey, United States, 07503
        • St. Joseph's Hospital and Medical Center
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Center
      • New York, New York, United States, 10016
        • NYU School of Medicine's Kaplan Comprehensive Cancer Center
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center, UNC
    • North Dakota
      • Fargo, North Dakota, United States, 58102
        • Veterans Affairs Medical Center - Fargo
      • Fargo, North Dakota, United States, 58122
        • CCOP - Merit Care Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Children's Hospital Medical Center - Cincinnati
      • Cleveland, Ohio, United States, 44106-5065
        • Ireland Cancer Center
      • Columbus, Ohio, United States, 43205-2696
        • Children's Hospital of Columbus
    • Oregon
      • Portland, Oregon, United States, 97201-3098
        • Doernbecher Children's Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213
        • Children's Hospital of Pittsburgh
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt-Ingram Cancer Center
    • Texas
      • Houston, Texas, United States, 77030-4009
        • University of Texas - MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Huntsman Cancer Institute
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center - Seattle
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Comprehensive Cancer Center

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 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Estimate the rate of BEACOPP )((Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone) specific toxicity in pediatric patients

Secondary Outcome Measures

Outcome Measure
Obtain preliminary estimates of response to BEACOPP ((Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone)

Collaborators and Investigators

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

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Kara Kelly, MD, Herbert Irving Comprehensive Cancer Center

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

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

October 1, 1999

Primary Completion (Actual)

October 1, 2003

Study Completion (Actual)

June 1, 2008

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

April 14, 2004

First Posted (Estimate)

April 15, 2004

Study Record Updates

Last Update Posted (Estimate)

February 26, 2014

Last Update Submitted That Met QC Criteria

February 25, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 59704
  • COG-59704 (Other Identifier: Children's Oncology Group)
  • CDR0000067222 (Other Identifier: ClinicalTrials.gov)

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.

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