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

Stage I Childhood Hodgkin Lymphoma Clinical Trial

Official title:

A Phase III Study for the Treatment of Children and Adolescents With Newly Diagnosed Low Risk Hodgkin Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00302003
• Other study ID #: AHOD0431
• Secondary ID: NCI-2009-00377CD
• Status: Completed
• Phase: Phase 3
• Start date: February 2006
• Est. completion date: June 30, 2019

Study information

• Verified date: August 2016
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 287
• Est. completion date: June 30, 2019
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Childhood Favorable Prognosis Hodgkin Lymphoma
• Childhood Lymphocyte Depletion Hodgkin Lymphoma
• Childhood Mixed Cellularity Hodgkin Lymphoma
• Childhood Nodular Sclerosis Hodgkin Lymphoma
• Hodgkin Disease
• Lymphoma
• Stage I Childhood Hodgkin Lymphoma
• Stage II Childhood Hodgkin Lymphoma

Intervention

Radiation:
• radiation therapy
Undergo radiation therapy

Drug:
• doxorubicin hydrochloride
Given IV
• vincristine sulfate
Given IV
• prednisone
Given orally
• cyclophosphamide
Given IV
• ifosfamide
Given IV
• vinorelbine tartrate
Given IV
• dexamethasone
Given IV
• etoposide phosphate
Given IV
• cisplatin
Given IV
• cytarabine
Given IV

Biological:
• filgrastim
Given IV or subcutaneously

Locations

Country	Name	City	State
United States	Children's Oncology Group	Arcadia	California

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival Without Receiving Radiation Therapy (EFSnoRT).	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).	At 60 months
Primary	Intensive Therapy Free Survival (ITFS).	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.	At 60 months
Primary	Event Free Survival (EFS)	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).	At 60 months
Secondary	Overall Survival	Survival is defined as time from study entry to death due to any cause. Patients alive at last contact where censored at last contact.	At 60 months

External Links

•   Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive