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Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma
This study is ongoing, but not recruiting participants.
First Received: March 9, 2006   Last Updated: April 14, 2009   History of Changes
Sponsors and Collaborators: Children's Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00302003
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving more than one drug (combination chemotherapy) and giving them together with radiation therapy may kill more cancer cells.

PURPOSE: This phase III trial is studying how well combination chemotherapy works when given before radiation therapy and/or additional chemotherapy in treating young patients with newly diagnosed Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Biological: filgrastim
Drug: cisplatin
Drug: cyclophosphamide
Drug: cytarabine
Drug: dexamethasone
Drug: doxorubicin hydrochloride
Drug: etoposide phosphate
Drug: ifosfamide
Drug: prednisone
Drug: vincristine sulfate
Drug: vinorelbine ditartrate
Radiation: radiation therapy
Phase III

MedlinePlus related topics: Cancer Hodgkin's Disease Lymphoma Radiation Therapy
Drug Information available for: Dexamethasone Cyclophosphamide Prednisone Vincristine Cytarabine hydrochloride Cisplatin Doxorubicin Doxorubicin hydrochloride Etoposide Dexamethasone acetate Vinorelbine Doxiproct plus Myocet Etoposide phosphate Filgrastim Vinorelbine tartrate Cytarabine Dexamethasone Sodium Phosphate Vincristine sulfate Ifosfamide
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase III Study for the Treatment of Children and Adolescents With Newly Diagnosed Low Risk Hodgkin's Disease

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Minimum time to a requirement for involved-field radiotherapy (IFRT), requirement for additional chemotherapy and IFRT for retrieval, occurrence of a second malignant neoplasm, or death from any cause [ Designated as safety issue: No ]
  • Minimum time to a relapse of higher risk at any time, any relapse following treatment with protocol-mandated IFRT, death from any cause, or the occurrence of a second malignant neoplasm [ Designated as safety issue: No ]
  • Minimum time to a relapse of any kind, death from any cause, or occurrence of a second malignant neoplasm [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to death [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: February 2006
Estimated Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Investigate the paradigm of response-based therapy for low-risk Hodgkin's lymphoma by eliminating involved-field radiotherapy (IFRT) in patients who achieve a complete remission (CR) after initial chemotherapy.
  • Investigate whether 3 courses of doxorubicin hydrochloride, vincristine, prednisone, and cyclophosphamide (AV-PC) for the treatment of low-risk Hodgkin's lymphoma is sufficient to induce CR in at least 80% of patients.
  • Investigate whether patients who experience a low-risk relapse after initial treatment with chemotherapy alone can be successfully treated with a salvage regimen comprising ifosfamide and vinorelbine ditartrate with dexamethasone, etoposide phosphate, cisplatin, and cytarabine (IV/DECA) and IFRT.
  • Maintain the overall survival for patients with low-risk Hodgkin's lymphoma at or above 97%.
  • Determine the prognostic significance of very early response as measured by fludeoxyglucose-positron emission tomography (FDG-PET) or gallium after the first course of chemotherapy.
  • Evaluate the prognostic significance of elevation of erythrocyte sedimentation rate and C-reactive protein at the time of diagnosis in patients with low-risk Hodgkin's lymphoma on CR rate and relapse rate after chemotherapy alone.
  • Determine the frequency and severity of late effects of therapy, including thyroid dysfunction, infertility, cardiotoxicity, and second malignant neoplasms.

OUTLINE: This is a multicenter study.

  • Initial chemotherapy: Patients receive doxorubicin hydrochloride IV over 10-30 minutes and cyclophosphamide IV over 1 hour on days 1-2, vincristine IV on days 1 and 8, oral prednisone on days 1-7, and filgrastim (G-CSF) subcutaneously (SC) on days 3-7 and 9-14. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission (CR) proceed to observation. Patients achieving partial remission proceed to radiotherapy. Patients who have a low-risk relapse after achieving CR on initial chemotherapy proceed to salvage chemotherapy followed by radiotherapy. Patients who have stable disease or disease progression go off study.
  • Salvage chemotherapy: Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1-5, and G-CSF SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients then receive dexamethasone IV over 15 minutes every 12 hours, etoposide phosphate IV over 3 hours every 12 hours, and cytarabine IV over 3 hours every 12 hours on days 1 and 2; cisplatin IV over 6 hours on day 1; and G-CSF SC or IV beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients then proceed to radiotherapy.
  • Involved-field radiotherapy (IFRT): Beginning 4 weeks after completion of chemotherapy, patients undergo IFRT once daily, 5 days a week, for 2.8 weeks. Patients who do not achieve CR go off study. After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed Hodgkin's lymphoma meeting the following criteria:

    • Newly diagnosed disease
    • Stage IA OR stage IIA without bulky disease

      • Bulky disease is defined as a large mediastinal mass or large extramediastinal nodal aggregate
    • No lymphocyte-predominant histology

PATIENT CHARACTERISTICS:

  • Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
  • Bilirubin ≤ 1.5 times normal
  • ALT ≤ 2.5 times normal
  • Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by MUGA
  • No pathologic prolongation of QTc interval on 12-lead ECG
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Negative pregnancy test

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy or radiotherapy
  • At least 30 days since prior systemic corticosteroids
  • No other concurrent cancer chemotherapy or immunomodulating agents (including steroids)
  • No concurrent corticosteroid therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00302003

  Show 187 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Frank G. Keller, MD Mary Babb Randolph Cancer Center at West Virginia University Hospitals
  More Information

Additional Information:
No publications provided

Responsible Party: Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers: CDR0000459962, COG-AHOD0431
Study First Received: March 9, 2006
Last Updated: April 14, 2009
ClinicalTrials.gov Identifier: NCT00302003     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage I childhood Hodgkin lymphoma
stage II childhood Hodgkin lymphoma
childhood lymphocyte depletion Hodgkin lymphoma
childhood mixed cellularity Hodgkin lymphoma
childhood nodular sclerosis Hodgkin lymphoma
childhood favorable prognosis Hodgkin lymphoma

Study placed in the following topic categories:
Anti-Inflammatory Agents
Antimetabolites
Dexamethasone
Prednisone
Immunologic Factors
Hodgkin Lymphoma, Childhood
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Vinblastine
Cyclophosphamide
Hormones
Etoposide phosphate
Anti-Bacterial Agents
Cisplatin
Alkylating Agents
Hodgkin Disease
Lymphoma
Etoposide
Dexamethasone acetate
Cytarabine
Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Hodgkin Lymphoma, Adult
Hodgkin's Disease
Vincristine
Sclerosis
Antimitotic Agents
Glucocorticoids
Antiviral Agents

Additional relevant MeSH terms:
Dexamethasone
Anti-Inflammatory Agents
Prednisone
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Vinblastine
Hormones
Therapeutic Uses
Etoposide
Hodgkin Disease
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents, Hormonal
Vincristine
Glucocorticoids
Doxorubicin
Neoplasms
Vinorelbine
Antineoplastic Agents, Phytogenic
Antimetabolites
Immunologic Factors
Antineoplastic Agents
Cyclophosphamide
Antibiotics, Antineoplastic
Etoposide phosphate
Lymphoma

ClinicalTrials.gov processed this record on May 07, 2009