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

NCT00002827 | Completed Phase 3 DMC

• 5 other identifiers: 9426POG-9426CCG-P9426CDR0000065013COG-9426
• Study Type: interventional
• Target: 294
• Locations: 3 countries
• Sites: 39

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.

Conditions

Cardiac Toxicity; Lymphoma

Keywords

stage II childhood Hodgkin lymphoma; stage I childhood Hodgkin lymphoma; stage III childhood Hodgkin lymphoma; cardiac toxicity

Outcome Measures

Primary Outcomes (1)

• DLCO

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

  1 year post therapy

Study Arms (2)

Treatment #1 (Without Zinecard)

EXPERIMENTAL

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; Biological: filgrastim; 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

Treatment #2 (with Zinecard)

EXPERIMENTAL

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; 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

Interventions

bleomycin sulfate BIOLOGICAL

Given IV

Also known as: Blenoxane, NSC #125066

Treatment #1 (Without Zinecard); Treatment #2 (with Zinecard)

filgrastim BIOLOGICAL

Given IV

Also known as: Granulocyte-colony stimulating factor, r-metHuG-CSF, G-CSF, Neupogen, NSC #614629

Treatment #1 (Without Zinecard); Treatment #2 (with Zinecard)

dexrazoxane hydrochloride DRUG

Given IV

Also known as: DZR, ADR-529, ZINECARD, ICRF-187, NSC #169780

Treatment #2 (with Zinecard)

doxorubicin hydrochloride DRUG

Given IV

Also known as: NSC #123127

Treatment #1 (Without Zinecard); Treatment #2 (with Zinecard)

etoposide DRUG

Given IV

Also known as: VP-16, VePesid, NSC #141540

Treatment #1 (Without Zinecard); Treatment #2 (with Zinecard)

vincristine sulfate DRUG

Given IV

Also known as: VCR, Oncovin, NSC #67574

Treatment #1 (Without Zinecard); Treatment #2 (with Zinecard)

low-LET cobalt-60 gamma ray therapy RADIATION

Treatment #1 (Without Zinecard); Treatment #2 (with Zinecard)

low-LET electron therapy RADIATION

Treatment #1 (Without Zinecard); Treatment #2 (with Zinecard)

low-LET photon therapy RADIATION

Treatment #1 (Without Zinecard); Treatment #2 (with Zinecard)

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

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

Study Sites (39)

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, 90095-1781, United States

Location

Children's Hospital of Orange County

Orange, California, 92668, United States

Location

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, 94115-0128, United States

Location

David Grant Medical Center

Travis Air Force Base, California, 94535, United States

Location

Children's Hospital of Denver

Denver, Colorado, 80218, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5265, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0752, United States

Location

CCOP - Kalamazoo

Kalamazoo, Michigan, 49007-3731, United States

Location

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Children's Mercy Hospital - Kansas City

Kansas City, Missouri, 64108, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-3330, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Kaplan Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, 27599-7295, United States

Location

Veterans Affairs Medical Center - Fargo

Fargo, North Dakota, 58102, United States

Location

CCOP - Merit Care Hospital

Fargo, North Dakota, 58122, United States

Location

Children's Hospital Medical Center - Cincinnati

Cincinnati, Ohio, 45229-3039, United States

Location

Ireland Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Children's Hospital of Columbus

Columbus, Ohio, 43205-2696, United States

Location

Doernbecher Children's Hospital

Portland, Oregon, 97201-3098, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt Cancer Center

Nashville, Tennessee, 37232-6838, United States

Location

University of Texas - MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84132, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792, United States

Location

Princess Margaret Hospital for Children

Perth, Western Australia, 6001, Australia

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

IWK Grace Health Centre

Halifax, Nova Scotia, B3J 3G9, Canada

Location

Related Publications (4)

• 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.

  PMID: 17290056 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.

  BACKGROUND

• Tebbi CK, Mendenhall NP, London WB, Williams JL, Hutchison RE, Fitzgerald TJ, de Alarcon PA, Schwartz C, Chauvenet A. Response-dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2012 Dec 15;59(7):1259-65. doi: 10.1002/pbc.24279. Epub 2012 Aug 21.

  PMID: 22911615 RESULT

• Mendenhall NP, Meyer J, Williams J, et al.: The impact of central quality assurance review prior to radiation therapy on protocol compliance: POG 9426, a trial in pediatric Hodgkin's disease. [Abstract] Blood 106 (11): A-753, 2005.

  RESULT

MeSH Terms

Conditions

Cardiotoxicity; Lymphoma

Interventions

Bleomycin; Filgrastim; Granulocyte Colony-Stimulating Factor; Dexrazoxane; Razoxane; Doxorubicin; Etoposide; Vincristine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Colony-Stimulating Factors; Glycoproteins; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Proteins; Biological Factors; Diketopiperazines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Cameron K. Tebbi, MD

  St. Joseph's Children's Hospital of Tampa

  STUDY CHAIR

• Michael A. Weiner, MD

  Herbert Irving Comprehensive Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: May 26, 2004
• Study Start: October 1, 1996
• Primary Completion: October 1, 2004
• Study Completion: June 1, 2008
• Last Updated: August 26, 2013

Record last verified: 2013-08

Locations

AU (1); CA (2); US (36)