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

This study has been completed.
Sponsor:
Collaborators:
Children's Cancer Group
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002827
First received: November 1, 1999
Last updated: August 22, 2013
Last verified: August 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • DLCO [ Time Frame: 1 year post therapy ] [ Designated as safety issue: No ]
    The Wilcoxon test will be used to evaluate whether DLCO values differ between the two arms.


Enrollment: 294
Study Start Date: October 1996
Study Completion Date: June 2008
Primary Completion Date: October 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002827

  Show 39 Study Locations
Sponsors and Collaborators
Children's Oncology Group
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
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00002827     History of Changes
Other Study ID Numbers: 9426, POG-9426, CCG-P9426, CDR0000065013, COG-9426
Study First Received: November 1, 1999
Last Updated: August 22, 2013
Health Authority: United States: Federal Government

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:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bleomycin
Doxorubicin
Etoposide phosphate
Etoposide
Razoxane
Vincristine
Lenograstim
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Cardiovascular Agents
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014