Clinical trial NCT00004010: Combination Chemotherapy and Radiation Therapy in Treating Children With Previously Untreated Stage II, Stage III, or Stage IV Hodgkin's Disease
Official title: Pilot Study for the Treatment of Children With Newly Diagnosed Advanced Stage Hodgkin's Disease: Upfront Dose Intensive Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: 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
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-15
Enrollment: 99
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Estimate the rate of BEACOPP )((Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone) specific toxicity in pediatric patients
Secondary outcomes:
measure: Obtain preliminary estimates of response to BEACOPP ((Bleomycin, Etoposide, Adriamycin, Cyclophosphamide, Vincristine, Procarbazine, Prednisone)
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: Travis Air Force Base
country: United States
facility: David Grant Medical Center
state: California
city: Denver
country: United States
facility: Children's Hospital of Denver
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Hospital and Medical Center
state: New Jersey
city: New York
country: United States
facility: NYU School of Medicine's Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Fargo
country: United States
facility: Veterans Affairs Medical Center - Fargo
state: North Dakota
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center - Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Ireland Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Children's Hospital of Columbus
state: Ohio
city: Portland
country: United States
facility: Doernbecher Children's Hospital
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
Study officials:
affiliation: Herbert Irving Comprehensive Cancer Center
name: Kara Kelly, MD
role: STUDY_CHAIR
References:
citation: Kelly KM, Sposto R, Hutchinson R, Massey V, McCarten K, Perkins S, Lones M, Villaluna D, Weiner M. BEACOPP chemotherapy is a highly effective regimen in children and adolescents with high-risk Hodgkin lymphoma: a report from the Children's Oncology Group. Blood. 2011 Mar 3;117(9):2596-603. doi: 10.1182/blood-2010-05-285379. Epub 2010 Nov 15.
citation: 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.
citation: 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.