Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00302003
Recruitment Status : Completed
First Posted : March 13, 2006
Results First Posted : February 9, 2017
Last Update Posted : March 30, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE March 9, 2006
First Posted Date  ICMJE March 13, 2006
Results First Submitted Date  ICMJE June 29, 2016
Results First Posted Date  ICMJE February 9, 2017
Last Update Posted Date March 30, 2021
Study Start Date  ICMJE February 2006
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2016)
  • Event Free Survival Without Receiving Radiation Therapy (EFSnoRT). [ Time Frame: At 60 months ]
    Survival is defined as the minimum time from study entry to requirement for additional chemotherapy and IFRT for retrieval, occurrence of a second malignant neoplasm, or death from any cause. Patients without report of such events where censored at last contact. Patients who achieve less than CR after 3 cycles of AV-PC will require IFRT and hence will satisfy this definition at the time of response evaluation. Patients who achieve a CR but who relapse will receive addition chemotherapy and IFRT or intense retrieval and hence will satisfy this definition at the time of the first relapse of Hodgkin disease. This endpoint will be used to compute event free survival without receiving radiation therapy (EFSnoRT).
  • Intensive Therapy Free Survival (ITFS). [ Time Frame: At 60 months ]
    Survival is defined as the minimum time from study entry 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. This will be used to compute intensive therapy free survival (ITFS). Patients without report of such events where censored at last contact. This differs from traditional EFS in that relapse after AVPC* x3 therapy alone that does not place the patient in a higher risk category is not considered a treatment failure. In this definition, higher-risk relapse refers to relapse involving sites and extent of disease that place the patient in the current COG definition of intermediate or high-risk disease. If a patient with CR who experiences a LR relapse is not retreated with protocol-mandated chemotherapy and IFRT, subsequent disease relapses will nevertheless be counted in the analysis of the treatment strategy.
  • Event Free Survival (EFS) [ Time Frame: At 60 months ]
    Survival is defined as the minimum time from study entry to a relapse of any kind, death from any cause, or occurrence of a second malignant neoplasm. Patients without report of such events where censored at last contact. This will be used to compute event free survival (EFS).
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2016)
Overall Survival [ Time Frame: At 60 months ]
Survival is defined as time from study entry to death due to any cause. Patients alive at last contact where censored at last contact.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma
Official Title  ICMJE A Phase III Study for the Treatment of Children and Adolescents With Newly Diagnosed Low Risk Hodgkin Disease
Brief Summary 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. 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.
Detailed Description

OBJECTIVES:

I. 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.

II. 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.

III. 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.

IV. Maintain the overall survival for patients with low-risk Hodgkin's lymphoma at or above 97%.

V. 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.

VI. 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.

VII. 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 intravenously (IV) over 10-30 minutes and cyclophosphamide IV over 1 hour on days 1-2, vincristine IV on days 1 and 8, prednisone orally (PO) 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Childhood Favorable Prognosis Hodgkin Lymphoma
  • Childhood Lymphocyte Depletion Hodgkin Lymphoma
  • Childhood Mixed Cellularity Hodgkin Lymphoma
  • Childhood Nodular Sclerosis Hodgkin Lymphoma
  • Stage I Childhood Hodgkin Lymphoma
  • Stage II Childhood Hodgkin Lymphoma
Intervention  ICMJE
  • Radiation: radiation therapy
    Undergo radiation therapy
    Other Names:
    • irradiation
    • radiotherapy
    • therapy, radiation
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Drug: prednisone
    Given orally
    Other Names:
    • DeCortin
    • Deltra
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: ifosfamide
    Given IV
    Other Names:
    • Cyfos
    • Holoxan
    • IFF
    • IFX
    • IPP
  • Drug: vinorelbine tartrate
    Given IV
    Other Names:
    • Eunades
    • navelbine ditartrate
    • NVB
    • VNB
  • Drug: dexamethasone
    Given IV
    Other Names:
    • Aeroseb-Dex
    • Decaderm
    • Decadron
    • DM
    • DXM
  • Drug: etoposide phosphate
    Given IV
    Other Names:
    • ETOP
    • Etopophos
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Drug: cytarabine
    Given IV
    Other Names:
    • ARA-C
    • arabinofuranosylcytosine
    • arabinosylcytosine
    • Cytosar-U
    • cytosine arabinoside
  • Biological: filgrastim
    Given IV or subcutaneously
    Other Names:
    • G-CSF
    • Neupogen
Study Arms  ICMJE Experimental: Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim
Treatment consists of 3 cycles of Doxorubicin hydrochloride IV (25 mg/m2) days 1 & 2, Vincristine sulfate IV (1.4 mg/m2 [max 2.8 mg]) Days 1 & 8, Prednisone orally (40 mg/m2) Days 1-7, Cyclophosphamide IV (600 mg/m2) Days 1 & 2, Filgrastim by mouth or IV (5 micrograms/kg/dose) 24 hours after Cyclophosphamide complete. See detailed description for remainder of therapy.
Interventions:
  • Radiation: radiation therapy
  • Drug: doxorubicin hydrochloride
  • Drug: vincristine sulfate
  • Drug: prednisone
  • Drug: cyclophosphamide
  • Drug: ifosfamide
  • Drug: vinorelbine tartrate
  • Drug: dexamethasone
  • Drug: etoposide phosphate
  • Drug: cisplatin
  • Drug: cytarabine
  • Biological: filgrastim
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 10, 2013)
287
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 30, 2019
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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

    • Newly diagnosed disease
    • Stage IA OR stage IIA without bulky disease
    • No lymphocyte-predominant histology
  • Staging on this study will be determined by the clinical stage; surgical staging is strongly discouraged, except for the rare situation of equivocal imaging studies below the diaphragm
  • Patients may not have received any previous chemotherapy or radiation therapy; patients may not have received systemic corticosteroids within 30 days of enrollment on this protocol; steroids used for treatment of contrast agent allergy required for computed tomography (CT) scans are acceptable
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^3
  • Total bilirubin =< 1.5 x normal
  • Alanine (ALT) =< 2.5 x normal
  • Shortening fraction >= 27% by echocardiogram OR ejection fraction >= 50% by multi-gated acquisition (MUGA)
  • No pathologic prolongation of QTc interval on 12-lead electrocardiography (ECG)
  • Female patients of childbearing potential must have a negative pregnancy test
  • Lactating females must agree that they will not breastfeed a child while on this study
  • Fertile patients must use effective contraception
  • Males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries Australia,   Canada,   Israel,   New Zealand,   Puerto Rico,   Switzerland
 
Administrative Information
NCT Number  ICMJE NCT00302003
Other Study ID Numbers  ICMJE AHOD0431
NCI-2009-00377 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000459962 ( Other Identifier: Clinical Trials.gov )
U10CA098543 ( U.S. NIH Grant/Contract )
COG-AHOD0431 ( Other Identifier: Children's Oncology Group )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Frank Keller, MD Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP