Clinical trial NCT00302003: Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma
Official title: A Phase III Study for the Treatment of Children and Adolescents With Newly Diagnosed Low Risk Hodgkin Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: 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
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-03-13
Enrollment: 287
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Event Free Survival Without Receiving Radiation Therapy (EFSnoRT).
timeFrame: At 60 months
measure: Intensive Therapy Free Survival (ITFS).
timeFrame: At 60 months
measure: Event Free Survival (EFS)
timeFrame: At 60 months
Secondary outcomes:
measure: Overall Survival
timeFrame: At 60 months
Other outcomes:
Locations:
city: Arcadia
country: United States
facility: Children's Oncology Group
state: California
Study officials:
affiliation: Children's Oncology Group
name: Frank Keller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Parekh A, Keller FG, McCarten KM, Kessel S, Cho S, Pei Q, Wu Y, Castellino SM, Constine LS, Schwartz CL, Hodgson D, Kelly KM, Hoppe BS. Targeted radiotherapy for early-stage, low-risk pediatric Hodgkin lymphoma slow early responders: a COG AHOD0431 analysis. Blood. 2022 Sep 8;140(10):1086-1093. doi: 10.1182/blood.2022016098.