Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Disease

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00002827
• Collaborator: National Cancer Institute (NCI) (NIH), Children's Cancer Group (Other)
• Enrollment: 294
• Locations: 39
• Arms: 2
• Duration (Months): 140
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Toxicity; Lymphoma	Biological: bleomycin sulfate; Biological: filgrastim; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: vincristine sulfate; Radiation: low-LET cobalt-60 gamma ray therapy; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 294 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: RESPONSE DEPENDENT TREATMENT OF STAGES IA, IIA AND IIIA HODGKIN'S DISEASE WITH DBVE AND LOW DOSE INVOLVED FIELD IRRADIATION WITH OR WITHOUT ZINECARD: A PEDIATRIC ONCOLOGY GROUP PHASE III STUDY
• Study Start Date: Oct 1, 1996
• Actual Primary Completion Date: Oct 1, 2004
• Actual Study Completion Date: Jun 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment #1 (Without Zinecard) 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).	Biological: bleomycin sulfate; Given IV; Other Names: Blenoxane NSC #125066 ; Biological: filgrastim; Given IV; Other Names: Granulocyte-colony stimulating factor r-metHuG-CSF G-CSF Neupogen NSC #614629 ; Drug: doxorubicin hydrochloride; Given IV; Other Names: NSC #123127 ; Drug: etoposide; Given IV; Other Names: VP-16 VePesid NSC #141540 ; Drug: vincristine sulfate; Given IV; Other Names: VCR Oncovin NSC #67574 ; Radiation: low-LET cobalt-60 gamma ray therapy; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy
Experimental: Treatment #2 (with Zinecard) 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	Biological: bleomycin sulfate; Given IV; Other Names: Blenoxane NSC #125066 ; Biological: filgrastim; Given IV; Other Names: Granulocyte-colony stimulating factor r-metHuG-CSF G-CSF Neupogen NSC #614629 ; Drug: dexrazoxane hydrochloride; Given IV; Other Names: DZR ADR-529 ZINECARD ICRF-187 NSC #169780 ; Drug: doxorubicin hydrochloride; Given IV; Other Names: NSC #123127 ; Drug: etoposide; Given IV; Other Names: VP-16 VePesid NSC #141540 ; Drug: vincristine sulfate; Given IV; Other Names: VCR Oncovin NSC #67574 ; Radiation: low-LET cobalt-60 gamma ray therapy; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy

Outcome Measures

Primary Outcome Measures

1. DLCO [1 year post therapy]

   The Wilcoxon test will be used to evaluate whether DLCO values differ between the two arms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS: Histologically proven Hodgkin's disease No more than 5 weeks since diagnostic biopsy No B symptoms Clinical/pathologic stages (all histologies) as follows: Stage IA/IIA with mediastinal mass less than one third of chest diameter Stage IIIA limited to spleen or splenic, celiac, or portal nodes and lesions no larger than 6 cm Surgical staging required if: Clinical and imaging findings equivocal Tanner stage IV/V for whom radiotherapy is planned Concurrent registration on protocols POG-8828 (late effects study) and POG- 8829 (epidemiology study) required

PATIENT CHARACTERISTICS: Age: 21 and under Performance status: Not specified Hematopoietic:

No hematopoietic disease Hepatic: No liver disease Renal: No renal disease Other: No severe organ or system damage or failure No pregnant or nursing women

PRIOR CONCURRENT THERAPY: No prior therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Long Beach Memorial Medical Center	Long Beach	California	United States	90806
2	Children's Hospital Los Angeles	Los Angeles	California	United States	90027-0700
3	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
4	Children's Hospital of Orange County	Orange	California	United States	92668
5	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94115-0128
6	David Grant Medical Center	Travis Air Force Base	California	United States	94535
7	Children's Hospital of Denver	Denver	Colorado	United States	80218
8	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
9	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637
10	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5265
11	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
12	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
13	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
14	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
15	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
16	Children's Mercy Hospital - Kansas City	Kansas City	Missouri	United States	64108
17	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-3330
18	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
19	Kaplan Cancer Center	New York	New York	United States	10016
20	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
21	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
22	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
23	Veterans Affairs Medical Center - Fargo	Fargo	North Dakota	United States	58102
24	CCOP - Merit Care Hospital	Fargo	North Dakota	United States	58122
25	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio	United States	45229-3039
26	Ireland Cancer Center	Cleveland	Ohio	United States	44106-5065
27	Children's Hospital of Columbus	Columbus	Ohio	United States	43205-2696
28	Doernbecher Children's Hospital	Portland	Oregon	United States	97201-3098
29	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
30	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
31	Vanderbilt Cancer Center	Nashville	Tennessee	United States	37232-6838
32	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030
33	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84132
34	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
35	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
36	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792
37	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
38	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
39	IWK Grace Health Centre	Halifax	Nova Scotia	Canada	B3J 3G9

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)
• Children's Cancer Group

Investigators

• Study Chair: Cameron K. Tebbi, MD, St. Joseph's Children's Hospital of Tampa
• Study Chair: Michael A. Weiner, MD, Herbert Irving Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00002827
• Other Study ID Numbers: 9426; POG-9426; CCG-P9426; CDR0000065013; COG-9426
• First Posted: May 26, 2004
• Last Update Posted: Aug 26, 2013
• Last Verified: Aug 1, 2013

• Keywords provided by Children's Oncology Group: stage II childhood Hodgkin lymphoma; stage I childhood Hodgkin lymphoma; stage III childhood Hodgkin lymphoma; cardiac toxicity
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Cardiotoxicity; Cobalt; Doxorubicin; Liposomal doxorubicin; Bleomycin; Etoposide; Dexrazoxane; Vincristine; Razoxane; Lenograstim

Study Results

No Results Posted as of Aug 26, 2013