Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Disease
- Conditions
- Cardiac ToxicityLymphoma
- Interventions
- Biological: bleomycin sulfateBiological: filgrastimRadiation: low-LET cobalt-60 gamma ray therapyRadiation: low-LET electron therapyRadiation: low-LET photon therapy
- Registration Number
- NCT00002827
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining chemotherapy with radiation therapy may kill more cancer cells. It is not yet known if chemotherapy is more effective with or without dexrazoxane for Hodgkin's disease.
PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy, with or without dexrazoxane, followed by radiation therapy in treating young patients with newly diagnosed stage I, stage II, or stage III Hodgkin's disease.
- Detailed Description
OBJECTIVES: I. Modify chemotherapy courses based on initial response to therapy in children with newly diagnosed stage IA/IIA/IIIA1 Hodgkin's disease. II. Examine the activity of variable courses of doxorubicin, bleomycin, vincristine, and etoposide (DBVE) followed by low-dose involved-field irradiation in these patients. III. Monitor the safety and feasibility of the response-dependent approach and the morbidity and immediate and long-term toxic effects associated with this regimen. IV. Assess whether limited therapy is adequate for patients with an early response. V. Evaluate whether the addition of dexrazoxane can reduce pulmonary toxicity while not significantly reducing the response rate or event-free survival. VI. Evaluate whether the frequency and magnitude of myocardial injury during therapy, as measured by elevated serum cardiac troponin-T, is reduced by the addition of dexrazoxane.
OUTLINE: This is a randomized study. Patients are stratified by participating institution. Patients are randomly assigned to receive doxorubicin, bleomycin, vincristine, etoposide, and filgrastim with vs. without dexrazoxane. Filgrastim SC begins on days 6-13; no filgrastim is given on day 14 or 15. Filgrastim will restart 2 days after completing therapy and continue until count recovery from expected nadir (ANC greater than 1000 cubic meter after nadir). Courses repeat every 28 days. Those with stable or responding disease after 2-4 courses receive involved-field radiotherapy 5 days per week for 3.5 weeks. Tanner stage IV/V patients are eligible for randomization based on a front-end institutional agreement and may receive standard-field radiotherapy 5 days per week for up to 11 weeks at the investigator's discretion. Patients are followed yearly until relapse, death, or for a minimum of 10 years.
PROJECTED ACCRUAL: A total of 285 patients will be accrued for this study over 5 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 294
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment #1 (Without Zinecard) vincristine sulfate All patients undergoing a splenectomy must receive penicillin or erythromycin prophylaxis twice a day. Pneumocystis prophylaxis:TMP/SMZ 150mg/m2(maximum 300 mg) of TMP in 2 divided doses on 3 consecutive days each week. Aerosolized Pentamidine (200mg/m2/dose - maximum dose 300 mg) should be substituted monthly for patients who cannot tolerate TMP/SMZ therapy. Continue pneumocystis prophylaxis for 6 months after stopping therapy. Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Bleomycin sulfate 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Vincristine sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Etoposide 10mg/m2/day 1-5. IV drip ( \< 0.4mg/ml) over 1 hour. Monitor blood pressure every 15 minutes during infusion. G-CSF (filgrastim) 5 mcg/Kg/day start on day 6 (24-36 hrs after 5th dose of VP16) and continued through day 13 (total 8 days). Treatment #1 (Without Zinecard) bleomycin sulfate All patients undergoing a splenectomy must receive penicillin or erythromycin prophylaxis twice a day. Pneumocystis prophylaxis:TMP/SMZ 150mg/m2(maximum 300 mg) of TMP in 2 divided doses on 3 consecutive days each week. Aerosolized Pentamidine (200mg/m2/dose - maximum dose 300 mg) should be substituted monthly for patients who cannot tolerate TMP/SMZ therapy. Continue pneumocystis prophylaxis for 6 months after stopping therapy. Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Bleomycin sulfate 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Vincristine sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Etoposide 10mg/m2/day 1-5. IV drip ( \< 0.4mg/ml) over 1 hour. Monitor blood pressure every 15 minutes during infusion. G-CSF (filgrastim) 5 mcg/Kg/day start on day 6 (24-36 hrs after 5th dose of VP16) and continued through day 13 (total 8 days). Treatment #1 (Without Zinecard) filgrastim All patients undergoing a splenectomy must receive penicillin or erythromycin prophylaxis twice a day. Pneumocystis prophylaxis:TMP/SMZ 150mg/m2(maximum 300 mg) of TMP in 2 divided doses on 3 consecutive days each week. Aerosolized Pentamidine (200mg/m2/dose - maximum dose 300 mg) should be substituted monthly for patients who cannot tolerate TMP/SMZ therapy. Continue pneumocystis prophylaxis for 6 months after stopping therapy. Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Bleomycin sulfate 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Vincristine sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Etoposide 10mg/m2/day 1-5. IV drip ( \< 0.4mg/ml) over 1 hour. Monitor blood pressure every 15 minutes during infusion. G-CSF (filgrastim) 5 mcg/Kg/day start on day 6 (24-36 hrs after 5th dose of VP16) and continued through day 13 (total 8 days). Treatment #1 (Without Zinecard) low-LET cobalt-60 gamma ray therapy All patients undergoing a splenectomy must receive penicillin or erythromycin prophylaxis twice a day. Pneumocystis prophylaxis:TMP/SMZ 150mg/m2(maximum 300 mg) of TMP in 2 divided doses on 3 consecutive days each week. Aerosolized Pentamidine (200mg/m2/dose - maximum dose 300 mg) should be substituted monthly for patients who cannot tolerate TMP/SMZ therapy. Continue pneumocystis prophylaxis for 6 months after stopping therapy. Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Bleomycin sulfate 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Vincristine sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Etoposide 10mg/m2/day 1-5. IV drip ( \< 0.4mg/ml) over 1 hour. Monitor blood pressure every 15 minutes during infusion. G-CSF (filgrastim) 5 mcg/Kg/day start on day 6 (24-36 hrs after 5th dose of VP16) and continued through day 13 (total 8 days). Treatment #1 (Without Zinecard) low-LET electron therapy All patients undergoing a splenectomy must receive penicillin or erythromycin prophylaxis twice a day. Pneumocystis prophylaxis:TMP/SMZ 150mg/m2(maximum 300 mg) of TMP in 2 divided doses on 3 consecutive days each week. Aerosolized Pentamidine (200mg/m2/dose - maximum dose 300 mg) should be substituted monthly for patients who cannot tolerate TMP/SMZ therapy. Continue pneumocystis prophylaxis for 6 months after stopping therapy. Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Bleomycin sulfate 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Vincristine sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Etoposide 10mg/m2/day 1-5. IV drip ( \< 0.4mg/ml) over 1 hour. Monitor blood pressure every 15 minutes during infusion. G-CSF (filgrastim) 5 mcg/Kg/day start on day 6 (24-36 hrs after 5th dose of VP16) and continued through day 13 (total 8 days). Treatment #1 (Without Zinecard) low-LET photon therapy All patients undergoing a splenectomy must receive penicillin or erythromycin prophylaxis twice a day. Pneumocystis prophylaxis:TMP/SMZ 150mg/m2(maximum 300 mg) of TMP in 2 divided doses on 3 consecutive days each week. Aerosolized Pentamidine (200mg/m2/dose - maximum dose 300 mg) should be substituted monthly for patients who cannot tolerate TMP/SMZ therapy. Continue pneumocystis prophylaxis for 6 months after stopping therapy. Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Bleomycin sulfate 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Vincristine sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Etoposide 10mg/m2/day 1-5. IV drip ( \< 0.4mg/ml) over 1 hour. Monitor blood pressure every 15 minutes during infusion. G-CSF (filgrastim) 5 mcg/Kg/day start on day 6 (24-36 hrs after 5th dose of VP16) and continued through day 13 (total 8 days). Treatment #2 (with Zinecard) bleomycin sulfate Zinecard (DZR) 250 mg/m2 IV push on days 1 and 15 before administration of doxorubicin and bleomycin sulfate. Give bleomycin sulfate and doxorubicin within 30 minutes of Zinecard (dexrazoxane hydrochloride). Bleomycin 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Vincristine Sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Treatment #2 (with Zinecard) filgrastim Zinecard (DZR) 250 mg/m2 IV push on days 1 and 15 before administration of doxorubicin and bleomycin sulfate. Give bleomycin sulfate and doxorubicin within 30 minutes of Zinecard (dexrazoxane hydrochloride). Bleomycin 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Vincristine Sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Treatment #2 (with Zinecard) dexrazoxane hydrochloride Zinecard (DZR) 250 mg/m2 IV push on days 1 and 15 before administration of doxorubicin and bleomycin sulfate. Give bleomycin sulfate and doxorubicin within 30 minutes of Zinecard (dexrazoxane hydrochloride). Bleomycin 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Vincristine Sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Treatment #2 (with Zinecard) vincristine sulfate Zinecard (DZR) 250 mg/m2 IV push on days 1 and 15 before administration of doxorubicin and bleomycin sulfate. Give bleomycin sulfate and doxorubicin within 30 minutes of Zinecard (dexrazoxane hydrochloride). Bleomycin 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Vincristine Sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Treatment #2 (with Zinecard) low-LET cobalt-60 gamma ray therapy Zinecard (DZR) 250 mg/m2 IV push on days 1 and 15 before administration of doxorubicin and bleomycin sulfate. Give bleomycin sulfate and doxorubicin within 30 minutes of Zinecard (dexrazoxane hydrochloride). Bleomycin 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Vincristine Sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Treatment #2 (with Zinecard) low-LET electron therapy Zinecard (DZR) 250 mg/m2 IV push on days 1 and 15 before administration of doxorubicin and bleomycin sulfate. Give bleomycin sulfate and doxorubicin within 30 minutes of Zinecard (dexrazoxane hydrochloride). Bleomycin 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Vincristine Sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Treatment #2 (with Zinecard) low-LET photon therapy Zinecard (DZR) 250 mg/m2 IV push on days 1 and 15 before administration of doxorubicin and bleomycin sulfate. Give bleomycin sulfate and doxorubicin within 30 minutes of Zinecard (dexrazoxane hydrochloride). Bleomycin 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Vincristine Sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Treatment #1 (Without Zinecard) doxorubicin hydrochloride All patients undergoing a splenectomy must receive penicillin or erythromycin prophylaxis twice a day. Pneumocystis prophylaxis:TMP/SMZ 150mg/m2(maximum 300 mg) of TMP in 2 divided doses on 3 consecutive days each week. Aerosolized Pentamidine (200mg/m2/dose - maximum dose 300 mg) should be substituted monthly for patients who cannot tolerate TMP/SMZ therapy. Continue pneumocystis prophylaxis for 6 months after stopping therapy. Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Bleomycin sulfate 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Vincristine sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Etoposide 10mg/m2/day 1-5. IV drip ( \< 0.4mg/ml) over 1 hour. Monitor blood pressure every 15 minutes during infusion. G-CSF (filgrastim) 5 mcg/Kg/day start on day 6 (24-36 hrs after 5th dose of VP16) and continued through day 13 (total 8 days). Treatment #1 (Without Zinecard) etoposide All patients undergoing a splenectomy must receive penicillin or erythromycin prophylaxis twice a day. Pneumocystis prophylaxis:TMP/SMZ 150mg/m2(maximum 300 mg) of TMP in 2 divided doses on 3 consecutive days each week. Aerosolized Pentamidine (200mg/m2/dose - maximum dose 300 mg) should be substituted monthly for patients who cannot tolerate TMP/SMZ therapy. Continue pneumocystis prophylaxis for 6 months after stopping therapy. Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Bleomycin sulfate 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Vincristine sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Etoposide 10mg/m2/day 1-5. IV drip ( \< 0.4mg/ml) over 1 hour. Monitor blood pressure every 15 minutes during infusion. G-CSF (filgrastim) 5 mcg/Kg/day start on day 6 (24-36 hrs after 5th dose of VP16) and continued through day 13 (total 8 days). Treatment #2 (with Zinecard) doxorubicin hydrochloride Zinecard (DZR) 250 mg/m2 IV push on days 1 and 15 before administration of doxorubicin and bleomycin sulfate. Give bleomycin sulfate and doxorubicin within 30 minutes of Zinecard (dexrazoxane hydrochloride). Bleomycin 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Vincristine Sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15 Treatment #2 (with Zinecard) etoposide Zinecard (DZR) 250 mg/m2 IV push on days 1 and 15 before administration of doxorubicin and bleomycin sulfate. Give bleomycin sulfate and doxorubicin within 30 minutes of Zinecard (dexrazoxane hydrochloride). Bleomycin 10 IU/m2/day IV push over 10 minutes on days 1 and 15 Doxorubicin hydrochloride 25mg/m2/day IV push over 15 minutes days 1 and 15 Vincristine Sulfate 1.5mg/m2/day IV push (maximum 2mg) days 1 and 15
- Primary Outcome Measures
Name Time Method DLCO 1 year post therapy The Wilcoxon test will be used to evaluate whether DLCO values differ between the two arms.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (39)
Children's Hospital of Columbus
🇺🇸Columbus, Ohio, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
Long Beach Memorial Medical Center
🇺🇸Long Beach, California, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Jonsson Comprehensive Cancer Center, UCLA
🇺🇸Los Angeles, California, United States
Children's Mercy Hospital - Kansas City
🇺🇸Kansas City, Missouri, United States
Kaplan Cancer Center
🇺🇸New York, New York, United States
Lineberger Comprehensive Cancer Center, UNC
🇺🇸Chapel Hill, North Carolina, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Herbert Irving Comprehensive Cancer Center
🇺🇸New York, New York, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Veterans Affairs Medical Center - Fargo
🇺🇸Fargo, North Dakota, United States
CCOP - Merit Care Hospital
🇺🇸Fargo, North Dakota, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
UCSF Cancer Center and Cancer Research Institute
🇺🇸San Francisco, California, United States
Children's Hospital of Denver
🇺🇸Denver, Colorado, United States
University of Minnesota Cancer Center
🇺🇸Minneapolis, Minnesota, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Indiana University Cancer Center
🇺🇸Indianapolis, Indiana, United States
Children's Hospital Medical Center - Cincinnati
🇺🇸Cincinnati, Ohio, United States
Ireland Cancer Center
🇺🇸Cleveland, Ohio, United States
Doernbecher Children's Hospital
🇺🇸Portland, Oregon, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
University of Texas - MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
David Grant Medical Center
🇺🇸Travis Air Force Base, California, United States
CCOP - Kalamazoo
🇺🇸Kalamazoo, Michigan, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Vanderbilt Cancer Center
🇺🇸Nashville, Tennessee, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
IWK Grace Health Centre
🇨🇦Halifax, Nova Scotia, Canada
University of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States