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| ID | Type | Description | Link |
|---|---|---|---|
| COG-9425 | Other Identifier | Children's Oncology Group | |
| CDR0000065359 | Other Identifier | Clinical Trials.gov | |
| P9425 | Other Identifier | Pediatric Oncology Group |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as dexrazoxane, may protect normal cells from the side effects of chemotherapy.
PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without dexrazoxane in treating children who have Hodgkin's disease.
OBJECTIVES: I. Determine the efficacy of doxorubicin, bleomycin, vincristine, etoposide, prednisone and cyclophosphamide (DBVE-PC) with filgrastim (G-CSF) followed by consolidative radiotherapy in children with advanced stage Hodgkin's disease. II. Tailor therapy based on rapidity of response in order to minimize cumulative drug dosages. III. Compare the efficacy of dexrazoxane in reducing pulmonary and cardiac toxicity of DBVE-based therapy without compromising response.
OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms. All patients receive 3 courses of chemotherapy consisting of doxorubicin and etoposide on days 0 and 1, bleomycin and vincristine on days 0 and 7, cyclophosphamide on day 0, and prednisone on days 0-6. Filgrastim (G-CSF) is administered on days 5-6 and 8-19. Each course is 21 days in length. Patients assigned to arm I receive only these drugs. Patients assigned to arm II receive dexrazoxane on days 0, 1, and 7 in addition to therapy as in arm I. Patients who exhibit a complete remission (CR) or provisional CR then receive radiotherapy to the regional field 5 days a week for 2.8 weeks. If the disease is not responsive, 2 more courses of chemotherapy are given. Patients whose disease remains nonresponsive or progresses go off the study. Radiotherapy may follow for others. Patients are followed every 3 months for the first year, every 4 months for the second year, every 6 months for the third year, and then annually thereafter.
PROJECTED ACCRUAL: A total of 277 patients will be accrued for this study within 3 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Experimental | Patients are randomized to one of two treatment arms. All patients receive 3 courses of chemotherapy consisting of doxorubicin hydrochloride and etoposide on days 0 and 1, bleomycin sulfate and vincristine sulfate on days 0 and 7, cyclophosphamide on day 0, and prednisone on days 0-6. Filgrastim (G-CSF) is administered on days 5-6 and 8-19. Each course is 21 days in length. Patients assigned to arm I receive only these drugs. |
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| Arm 2 | Experimental | Patients are randomized to one of two treatment arms. All patients receive 3 courses of chemotherapy consisting of doxorubicin hydrochloride and etoposide on days 0 and 1, bleomycin sulfate and vincristine sulfate on days 0 and 7, cyclophosphamide on day 0, and prednisone on days 0-6. Filgrastim (G-CSF) is administered on days 5-6 and 8-19. Each course is 21 days in length. Dexrazoxane hydrochloride on days 0, 1, and 7 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| bleomycin sulfate | Biological |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Diffusing capacity of the lungs for carbon monoxide (DLCO) | The Wilcoxon test will be used to evaluate whether DLCO values differ between the two arms. | One year post therapy |
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DISEASE CHARACTERISTICS: Histologically proven Hodgkin's disease of the following stages: Stages IIB, IIIB or IV
PATIENT CHARACTERISTICS: Age: 21 or under Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 2 times upper normal limit Renal: Not specified Other: Not pregnant
PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy Chemotherapy: No prior chemotherapy Endocrine therapy: Less than one week of steroids for management of airway complications Radiotherapy: No prior radiotherapy except emergency radiation to the mediastinum Surgery: Not specified
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| Name | Affiliation | Role |
|---|---|---|
| Cindy Schwartz, MD | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama Comprehensive Cancer Center | Birmingham | Alabama | 35294 | United States | ||
| MBCCOP - University of South Alabama |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17290056 | Background | Tebbi CK, London WB, Friedman D, Villaluna D, De Alarcon PA, Constine LS, Mendenhall NP, Sposto R, Chauvenet A, Schwartz CL. Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. J Clin Oncol. 2007 Feb 10;25(5):493-500. doi: 10.1200/JCO.2005.02.3879. | |
| Background | Schwartz CL, Tebbi CK, Constine LS: Response based therapy for pediatric Hodgkin's disease (HD): Pediatric Oncology Group (POG) protocols 9425/9426. [Abstract] Med Pediatr Oncol 37 (3): A-P219, 263, 2001. | ||
| 22689804 |
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| filgrastim |
| Biological |
|
|
| cyclophosphamide | Drug |
|
|
| dexrazoxane hydrochloride | Drug |
|
|
| doxorubicin hydrochloride | Drug |
|
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| etoposide | Drug |
|
|
| prednisone | Drug |
|
|
| vincristine sulfate | Drug |
|
|
| radiation therapy | Radiation |
|
| Mobile |
| Alabama |
| 36688 |
| United States |
| University of Arkansas for Medical Sciences | Little Rock | Arkansas | 72205 | United States |
| University of California San Diego Cancer Center | La Jolla | California | 92093-0658 | United States |
| Lucile Packard Children's Hospital at Stanford | Palo Alto | California | 94304 | United States |
| University of California Davis Medical Center | Sacramento | California | 95817 | United States |
| Yale Comprehensive Cancer Center | New Haven | Connecticut | 06520-8028 | United States |
| Walter Reed Army Medical Center | Washington D.C. | District of Columbia | 20307-5000 | United States |
| Shands Hospital and Clinics, University of Florida | Gainesville | Florida | 32610-100277 | United States |
| Sylvester Cancer Center, University of Miami | Miami | Florida | 33136 | United States |
| Miami Children's Hospital | Miami | Florida | 33155 | United States |
| CCOP - Florida Pediatric | Tampa | Florida | 33682-7757 | United States |
| Emory University Hospital - Atlanta | Atlanta | Georgia | 30322 | United States |
| Cancer Research Center of Hawaii | Honolulu | Hawaii | 96813 | United States |
| Children's Memorial Hospital, Chicago | Chicago | Illinois | 60614 | United States |
| University of Kansas Medical Center | Kansas City | Kansas | 66160-7357 | United States |
| CCOP - Wichita | Wichita | Kansas | 67214-3882 | United States |
| MBCCOP - LSU Medical Center | New Orleans | Louisiana | 70112 | United States |
| CCOP - Ochsner | New Orleans | Louisiana | 70121 | United States |
| Ochsner Clinic | New Orleans | Louisiana | 70121 | United States |
| Marlene & Stewart Greenebaum Cancer Center, University of Maryland | Baltimore | Maryland | 21201 | United States |
| Johns Hopkins Oncology Center | Baltimore | Maryland | 21231 | United States |
| Boston Floating Hospital Infants and Children | Boston | Massachusetts | 02111 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| University of Massachusetts Memorial Medical Center | Worcester | Massachusetts | 01655 | United States |
| Children's Hospital of Michigan | Detroit | Michigan | 48201 | United States |
| University of Mississippi Medical Center | Jackson | Mississippi | 39216-4505 | United States |
| Cardinal Glennon Children's Hospital | St Louis | Missouri | 63104 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| CCOP - Northern New Jersey | Hackensack | New Jersey | 07601 | United States |
| Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| Roswell Park Cancer Institute | Buffalo | New York | 14263-0001 | United States |
| Schneider Children's Hospital | New Hyde Park | New York | 11042 | United States |
| Mount Sinai School of Medicine | New York | New York | 10029 | United States |
| University of Rochester Cancer Center | Rochester | New York | 14642 | United States |
| State University of New York - Upstate Medical University | Syracuse | New York | 13210 | United States |
| Memorial Mission Hospital | Asheville | North Carolina | 28801 | United States |
| Carolinas Medical Center | Charlotte | North Carolina | 28232-2861 | United States |
| Presbyterian Healthcare | Charlotte | North Carolina | 28233-3549 | United States |
| Duke Comprehensive Cancer Center | Durham | North Carolina | 27710 | United States |
| East Carolina University School of Medicine | Greenville | North Carolina | 27858-4354 | United States |
| Comprehensive Cancer Center of Wake Forest University Baptist Medical Center | Winston-Salem | North Carolina | 27157-1082 | United States |
| Oklahoma Memorial Hospital | Oklahoma City | Oklahoma | 73126-0307 | United States |
| CCOP - Columbia River Program | Portland | Oregon | 97213 | United States |
| St. Christopher's Hospital for Children | Philadelphia | Pennsylvania | 19134-1095 | United States |
| Rhode Island Hospital | Providence | Rhode Island | 02903 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425-0721 | United States |
| Children's Hospital of Greenville Hospital System | Greenville | South Carolina | 29605 | United States |
| Saint Jude Children's Research Hospital | Memphis | Tennessee | 38105-2794 | United States |
| Simmons Cancer Center - Dallas | Dallas | Texas | 75235-9154 | United States |
| Baylor College of Medicine | Houston | Texas | 77030 | United States |
| MBCCOP - South Texas Pediatric | San Antonio | Texas | 78284-7810 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78284-7811 | United States |
| Cancer Center, University of Virginia HSC | Charlottesville | Virginia | 22908 | United States |
| Naval Medical Center, Portsmouth | Portsmouth | Virginia | 23708-2197 | United States |
| Massey Cancer Center | Richmond | Virginia | 23298-0037 | United States |
| Midwest Children's Cancer Center | Milwaukee | Wisconsin | 53226 | United States |
| Cross Cancer Institute | Edmonton | Alberta | T6G 1Z2 | Canada |
| McMaster Division | Hamilton | Ontario | L8N 3Z5 | Canada |
| Hospital for Sick Children | Toronto | Ontario | M5G 1X8 | Canada |
| Montreal Children's Hospital | Montreal | Quebec | H3H 1P3 | Canada |
| Hopital Sainte Justine | Montreal | Quebec | H3T 1C5 | Canada |
| Swiss Pediatric Oncology Group Bern | Bern | CH 3010 | Switzerland |
| Result |
| Voss SD, Chen L, Constine LS, Chauvenet A, Fitzgerald TJ, Kaste SC, Slovis T, Schwartz CL. Surveillance computed tomography imaging and detection of relapse in intermediate- and advanced-stage pediatric Hodgkin's lymphoma: a report from the Children's Oncology Group. J Clin Oncol. 2012 Jul 20;30(21):2635-40. doi: 10.1200/JCO.2011.40.7841. Epub 2012 Jun 11. |
| 19584400 | Result | Schwartz CL, Constine LS, Villaluna D, London WB, Hutchison RE, Sposto R, Lipshultz SE, Turner CS, deAlarcon PA, Chauvenet A. A risk-adapted, response-based approach using ABVE-PC for children and adolescents with intermediate- and high-risk Hodgkin lymphoma: the results of P9425. Blood. 2009 Sep 3;114(10):2051-9. doi: 10.1182/blood-2008-10-184143. Epub 2009 Jul 7. |
| Result | Constine LS, Marcus R, Chauvenet A, et al.: Patterns of failure after response-based, dose-dense therapy for intermediate/high risk pediatric Hodgkin's disease (POG 9425). [Abstract] Int J Radiat Oncol Biol Phys 63 (Suppl 1): A-37, S21, 2005. |
| Result | Schwartz CL, Constine LS, London W, et al.: POG 9425: response-based, intensively timed therapy for intermediate/high stage (IS/HS) pediatric Hodgkin's disease. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1555, 2002. |
| ID | Term |
|---|---|
| D066126 | Cardiotoxicity |
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D001761 | Bleomycin |
| D000069585 | Filgrastim |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D003520 | Cyclophosphamide |
| D064730 | Dexrazoxane |
| D011929 | Razoxane |
| D004317 | Doxorubicin |
| D005047 | Etoposide |
| D011241 | Prednisone |
| D014750 | Vincristine |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D006020 | Glycopeptides |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D054659 | Diketopiperazines |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D005960 | Glucosides |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D013812 | Therapeutics |
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