Chemotherapy With or Without Additional Chemotherapy and/or Radiation Therapy in Treating Children With Newly Diagnosed Hodgkin's Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00025259
First received: October 11, 2001
Last updated: October 25, 2013
Last verified: October 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. It is not yet known if chemotherapy is more effective with or without additional chemotherapy and/or radiation therapy in treating Hodgkin's disease.

PURPOSE: This randomized phase III trial is studying different chemotherapy regimens given with or without radiation therapy to compare how well they work in treating children with newly diagnosed Hodgkin's disease.


Condition Intervention Phase
Lymphoma
Biological: bleomycin sulfate
Biological: filgrastim
Drug: cisplatin
Drug: cyclophosphamide
Drug: cytarabine
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: prednisone
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Group-Wide Study of Dose-Intensive Response-Based Chemotherapy and Radiation Therapy for Children and Adolescents With Newly Diagnosed Intermediate Risk Hodgkin Disease

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Event-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Event-free survival defined as the time to treatment failure (disease progression, disease recurrence, biopsy positive residual after completion of all protocol therapy), occurrence of a second malignant neoplasm, or death from any cause


Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Disease response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    assessed by modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria

  • Toxicity [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Incidence of Grade 3 or 4 non-hematologic toxicity that doesn't respond to treatment within 7 days despite recommended therapy modification assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0


Enrollment: 1734
Study Start Date: September 2002
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All patients-off therapy before callback-Induction only
Patients receive ABVE-PC (doxorubicin hydrochloride[A] IV (25mg/m²/day Day 1 & 2), bleomycin sulfate[B] IV (5 U/m2/day Day 1, 10 U/m2/day Day 8), vincristine sulfate [V] (1.4 mg/m2/day Days 1 & 8), etoposide[E] IV (125 mg/m²/day Days 1,2 &3), prednisone[P] (40 mg/m2/day Days 1-7), cyclophosphamide[C] IV (800mg/m2/day Day 1). Patients also receive filgrastim (G-CSF - 5 ug/kg/day) subcutaneously 24 hrs after Etoposide) and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Biological: bleomycin sulfate
Given IV or subcutaneously
Other Names:
  • Blenoxane
  • Bleocin
  • Bleocris
  • Bleolem
  • Bleomicina
  • Cytorich
  • NSC #125066
Biological: filgrastim
Given subcutaneously
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC614629
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC26271
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: etoposide
Given IV
Other Names:
  • VePesid
  • Etopophos
  • VP-16
  • NSC141540
Drug: prednisone
Given orally
Other Names:
  • Deltasone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC010023
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Experimental: RER with Complete Response - IFRT (Standard Arm)
Patients receive ABVE-PC (doxorubicin hydrochloride[A] IV (25mg/m²/day Day 1 & 2), bleomycin sulfate[B] IV (5 U/m2/day Day 1, 10 U/m2/day Day 8), vincristine sulfate [V] (1.4 mg/m2/day Days 1 & 8), etoposide[E] IV (125 mg/m²/day Days 1,2 &3), prednisone[P] (40 mg/m2/day Days 1-7), cyclophosphamide[C] IV (800mg/m2/day Day 1). Patients also receive filgrastim (G-CSF - 5 ug/kg/day) subcutaneously 24 hrs after Etoposide) and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After these 2 courses, patients then receive 2 additional courses of (ABVE-PC). If CR then randomized to Involved Field Radiation Therapy (IFRT).
Biological: bleomycin sulfate
Given IV or subcutaneously
Other Names:
  • Blenoxane
  • Bleocin
  • Bleocris
  • Bleolem
  • Bleomicina
  • Cytorich
  • NSC #125066
Biological: filgrastim
Given subcutaneously
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC614629
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC26271
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: etoposide
Given IV
Other Names:
  • VePesid
  • Etopophos
  • VP-16
  • NSC141540
Drug: prednisone
Given orally
Other Names:
  • Deltasone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC010023
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Patients undergo radiotherapy.
Experimental: RER with Complete Response - no IFRT ( Reduced Therapy Arm)
Patients receive ABVE-PC (doxorubicin hydrochloride[A] IV (25mg/m²/day Day 1 & 2), bleomycin sulfate[B] IV (5 U/m2/day Day 1, 10 U/m2/day Day 8), vincristine sulfate [V] (1.4 mg/m2/day Days 1 & 8), etoposide[E] IV (125 mg/m²/day Days 1,2 &3), prednisone[P] (40 mg/m2/day Days 1-7), cyclophosphamide[C] IV (800mg/m2/day Day 1). Patients also receive filgrastim (G-CSF - 5 ug/kg/day) subcutaneously 24 hrs after Etoposide) and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After these 2 courses, patients then receive 2 additional courses of (ABVE-PC). If CR then randomized to no further treatment.
Biological: bleomycin sulfate
Given IV or subcutaneously
Other Names:
  • Blenoxane
  • Bleocin
  • Bleocris
  • Bleolem
  • Bleomicina
  • Cytorich
  • NSC #125066
Biological: filgrastim
Given subcutaneously
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC614629
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC26271
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: etoposide
Given IV
Other Names:
  • VePesid
  • Etopophos
  • VP-16
  • NSC141540
Drug: prednisone
Given orally
Other Names:
  • Deltasone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC010023
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Experimental: RER with Progressive Disease - Off Therapy
Patients receive ABVE-PC (doxorubicin hydrochloride[A] IV (25mg/m²/day Day 1 & 2), bleomycin sulfate[B] IV (5 U/m2/day Day 1, 10 U/m2/day Day 8), vincristine sulfate [V] (1.4 mg/m2/day Days 1 & 8), etoposide[E] IV (125 mg/m²/day Days 1,2 &3), prednisone[P] (40 mg/m2/day Days 1-7), cyclophosphamide[C] IV (800mg/m2/day Day 1). Patients also receive filgrastim (G-CSF - 5 ug/kg/day) subcutaneously 24 hrs after Etoposide) and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After these 2 courses, patients then receive 2 additional courses of (ABVE-PC). Progressive disease and off protocol therapy.
Biological: bleomycin sulfate
Given IV or subcutaneously
Other Names:
  • Blenoxane
  • Bleocin
  • Bleocris
  • Bleolem
  • Bleomicina
  • Cytorich
  • NSC #125066
Biological: filgrastim
Given subcutaneously
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC614629
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC26271
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: etoposide
Given IV
Other Names:
  • VePesid
  • Etopophos
  • VP-16
  • NSC141540
Drug: prednisone
Given orally
Other Names:
  • Deltasone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC010023
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Experimental: SER - randomized to DECAX2 + ABVE-PCX2 + IFRT
Patients receive ABVE-PC (doxorubicin hydrochloride[A] IV (25mg/m²/day Day 1 & 2), bleomycin sulfate[B] IV (5 U/m2/day Day 1, 10 U/m2/day Day 8), vincristine sulfate [V] (1.4 mg/m2/day Days 1 & 8), etoposide[E] IV (125 mg/m²/day Days 1,2 &3), prednisone[P] (40 mg/m2/day Days 1-7), cyclophosphamide[C] IV (800mg/m2/day Day 1). Patients also receive filgrastim (G-CSF - 5 ug/kg/day) subcutaneously 24 hrs after Etoposide) and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After these 2 courses, Slow Early Response patients randomized will receive 2 cycles of Dexamethasone (10 mg/m2 Day 1&2), etoposide[E] IV (100 mg/m²/day Days 1&2), Cytarabine (3000 mg/m2) Day 1&2), Cisplatin (90 mg/m2 Day 1). Patients then receive 2 additional courses of (ABVE-PC) and Involved Field Radiation Therapy (IFRT).
Biological: bleomycin sulfate
Given IV or subcutaneously
Other Names:
  • Blenoxane
  • Bleocin
  • Bleocris
  • Bleolem
  • Bleomicina
  • Cytorich
  • NSC #125066
Biological: filgrastim
Given subcutaneously
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC614629
Drug: cisplatin
Given IV
Other Names:
  • Cis-diamminedichloroplatinum II
  • CDDP
  • cis-DDP
  • Platinol-AQ
  • NSC #119875
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC26271
Drug: cytarabine
Given IV
Other Names:
  • cytosine arabinoside
  • Ara-C
  • Cytosar
  • NSC #063878
Drug: dexamethasone
Given IV
Other Names:
  • Decadron
  • Hexadrol
  • Dexone
  • Dexameth
  • NSC #34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: etoposide
Given IV
Other Names:
  • VePesid
  • Etopophos
  • VP-16
  • NSC141540
Drug: prednisone
Given orally
Other Names:
  • Deltasone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC010023
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Patients undergo radiotherapy.
Experimental: SER - randomized to ABVE-PCX2 + IFRT
Patients receive ABVE-PC (doxorubicin hydrochloride[A] IV (25mg/m²/day Day 1 & 2), bleomycin sulfate[B] IV (5 U/m2/day Day 1, 10 U/m2/day Day 8), vincristine sulfate [V] (1.4 mg/m2/day Days 1 & 8), etoposide[E] IV (125 mg/m²/day Days 1,2 &3), prednisone[P] (40 mg/m2/day Days 1-7), cyclophosphamide[C] IV (800mg/m2/day Day 1). Patients also receive filgrastim (G-CSF - 5 ug/kg/day) subcutaneously 24 hrs after Etoposide) and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After these 2 courses, Slow Early Response patients randomized will receive 2 additional courses of (ABVE-PC) and Involved Field Radiation Therapy (IFRT).
Biological: bleomycin sulfate
Given IV or subcutaneously
Other Names:
  • Blenoxane
  • Bleocin
  • Bleocris
  • Bleolem
  • Bleomicina
  • Cytorich
  • NSC #125066
Biological: filgrastim
Given subcutaneously
Other Names:
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • G-CSF
  • Neupogen
  • NSC614629
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC26271
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Drug: etoposide
Given IV
Other Names:
  • VePesid
  • Etopophos
  • VP-16
  • NSC141540
Drug: prednisone
Given orally
Other Names:
  • Deltasone
  • Meticorten
  • Orasone
  • Liquid Pred
  • Pediapred
  • Sterapred
  • NSC010023
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • VCR
  • LCR
  • NSC #67574
Radiation: radiation therapy
Patients undergo radiotherapy.

Detailed Description:

OBJECTIVES:

  • Compare response-based therapy with doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide with or without dexamethasone, etoposide, cytarabine, cisplatin, and/or radiotherapy in children with intermediate-risk Hodgkin's lymphoma.
  • Determine whether radiotherapy can be eliminated from this regimen based upon early and complete response to multiagent chemotherapy in these patients.
  • Determine whether the addition of dexamethasone, etoposide, cytarabine, cisplatin, and filgrastim (G-CSF) improves outcome in those patients with a slow early response to standard chemotherapy.
  • Compare the frequency and severity of late effects of this therapy, including thyroid dysfunction, infertility, cardiotoxicity, pulmonary toxicity, and second malignant neoplasms, in patients treated with these regimens.
  • Correlate results from biology and late effects studies with response to therapy, event-free survival, and overall survival in these patients.

OUTLINE: This is a randomized, multicenter study.

ABVE-PC (A=Doxorubicin Hydrochloride, B=Bleomycin, V=Vincristine Sulfate, E=Etoposide, P=Prednisone, C=Cyclophosphamide, Initial chemotherapy (ABVE-PC): Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or subcutaneously (SC) and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 4 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease.

At the end of initial chemotherapy, patients undergo evaluation for response. Patients with less than 60% disease reduction are considered to have slow early response (SER). Patients with 60% or more disease reduction are considered to have rapid early response (RER).

  • RER: Patients with RER receive 2 additional courses of ABVE-PC chemotherapy. After the additional course, patients with less than a complete response undergo radiotherapy 5 days a week. Patients with a complete response are randomized to receive either radiotherapy or no further treatment.
  • SER: Patients with SER are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2 and cisplatin IV over 6 hours on day 1. Patients also receive G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After these 2 courses, patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients then undergo radiotherapy.
    • Arm II: Patients receive 2 additional courses of ABVE-PC chemotherapy. Patients then undergo radiotherapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study within 5-5.5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed newly diagnosed Hodgkin's lymphoma

    • All histologies eligible
    • Stage IB or IIB
    • Stage IA with bulk disease
    • Stage IIA with bulk disease
    • Stage IIAE
    • Stage IIIA
    • Stage IVA
  • May not be staged by laparotomy alone

    • Surgically staged patients must also have presurgical staging

PATIENT CHARACTERISTICS:

Age:

  • 21 and under

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Bilirubin no greater than 1.5 times normal
  • SGOT or SGPT less than 2.5 times normal

Renal:

  • Creatinine no greater than 1.5 times normal
  • Creatinine clearance greater than 40 mL/min OR
  • Radioisotope glomerular filtration rate greater than 70 mL/min

Cardiovascular:

  • Shortening fraction at least 27% by echocardiogram OR
  • Ejection fraction at least 50% by MUGA
  • No pathologic prolongation of QTc interval on 12-lead electrocardiogram

Pulmonary:

  • FEV_1/FVC greater than 60% by pulmonary function test OR
  • Pulse oximetry greater than 94% AND
  • No evidence of dyspnea at rest AND
  • No exercise intolerance

Other:

  • Adequate venous access
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • At least 1 month since prior corticosteroids except prednisone for respiratory distress

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • See Disease Characteristics
  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: NCT00025259

  Show 200 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Debra L. Friedman, MD, MS Seattle Children's Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00025259     History of Changes
Other Study ID Numbers: AHOD0031, COG-AHOD0031, CDR0000068943
Study First Received: October 11, 2001
Last Updated: October 25, 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
stage IV childhood Hodgkin lymphoma
childhood lymphocyte predominant Hodgkin lymphoma
childhood lymphocyte depletion Hodgkin lymphoma
childhood nodular sclerosis Hodgkin lymphoma
childhood mixed cellularity Hodgkin lymphoma
childhood nodular lymphocyte predominant Hodgkin lymphoma

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Etoposide phosphate
Liposomal doxorubicin
Cisplatin
Cyclophosphamide
Dexamethasone
Vincristine
Etoposide
Cytarabine
Doxorubicin
Prednisone
Bleomycin
Lenograstim
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2014