Combination Chemotherapy Plus Low-Dose Radiation Therapy in Treating Patients With Stage I or Stage IIA Hodgkin's Lymphoma

Lymphoma Clinical Trial

Official title:

Risk-Adapted Stanford V-C With Radiotherapy for Clinical Stage I and IIA Favorable Hodgkin's Disease: The G5 Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00026208
• Other study ID #: IRB-13081
• Secondary ID: LYMHD0002
• Status: Completed
• Phase: Phase 2
• Start date: June 2001
• Est. completion date: February 13, 2017

Study information

• Verified date: June 2018
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: This phase 2 trial is studying how well giving combination chemotherapy together with low-dose radiation therapy works in treating patients with stage I or stage IIA Hodgkin's lymphoma.

Description:

OBJECTIVES:

• Evaluate the freedom from progression in patients with stage I or IIA Hodgkin's lymphoma with a favorable prognosis treated with "Stanford V-C" chemotherapy comprising cyclophosphamide, doxorubicin, vinblastine, prednisone, vincristine, bleomycin, and etoposide with low-dose radiotherapy (RT).

• Minimize the early and late effects of treatment in these patients by avoiding staging laparotomy and its consequences, limiting cumulative doses of chemotherapy, and reducing the dose of RT to moderately bulky sites of disease.

• Assess early and late treatment-related toxicity, freedom from second disease progression, and overall survival at 5 and 10 years in patients treated with this regimen.

Participants receive Stanford V-C chemotherapy comprising cyclophosphamide IV over 30 to 60 minutes weekly on weeks 1 and 5; doxorubicin IV and vinblastine IV over 5 minutes once weekly on weeks 1, 3, 5, and 7; oral prednisone every other day on weeks 1 to 8; vincristine IV, and bleomycin IV over 5 minutes once weekly on weeks 2, 4, 6, and 8; and etoposide IV over 60 minutes on days 1 and 2 of weeks 3 and 7. Prior to protocol amendment, participants were assigned to treatment on the basis of tumor size (< 5 cm vs 5 to 10 cm), with only the participants with larger tumors receiving RT. Beginning 2 to 3 weeks after completion of chemotherapy, participants in the +RT group will receive low-dose radiotherapy 5 days a week for approximately 3 weeks. Subsequent to amendment, all participants received RT.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: February 13, 2017
• Est. primary completion date: April 26, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

INCLUSION CRITERIA:

• Diagnosis of previously untreated stage I or IIA Hodgkin's lymphoma, eligible subtypes

• Nodular sclerosis

• Mixed cellularity

• Classical, not otherwise specified

• Age = 18 years and = 70 years

• Granulocytes = 2 x 10e6/µL

• Platelets = 150 x 10e6/µL

• Bilirubin = 2.5 mg/dL

• Serum creatinine = 2 mg/dL

• Patients > 50 years or those with a history of cardiac disease should have an ejection fraction = 50%

• All scans, X-rays, laboratory tests must be performed within 6 weeks of enrollment

• Pathologic material reviewed at Stanford University

• Evaluation by Stanford Medical Oncology and Radiation Oncology with review at the Hodgkin's Disease Staging Conference

• Written informed consent

EXCLUSION CRITERIA:

• Lymphocytic predominance Hodgkin's disease

• Prior treatment for Hodgkin's disease

• Mediastinal mass equal to or greater than one-third the maximum intrathoracic diameter on a standing posteroanterior chest x-ray

• Any lymph node mass > 10 cm in greatest trans-axial diameter

• Two or more extranodal sites of disease

• Constitutional (B) symptoms present at diagnosis

• Prior or concurrent malignancies within 5 years (EXCEPTION: basal cell carcinoma of the skin)

• Any medical contraindication to the planned treatment, including:

• Pregnant

• Positive antibody test for the human immunodeficiency virus (HIV)

Related Conditions & MeSH terms

• Hodgkin Disease
• Lymphoma
• Lymphoma, Hodgkin Disease
• Lymphoma: Hodgkin

Intervention

Drug:
• Vincristine
1.4 mg/m² intravenously (IV) on week 2, 4, 6, 8
• Cyclophosphamide
650 mg/m², on week 1 and 5
• Doxorubicin
25 mg/m², on week 1, 3, 5, 7
• Prednisone
40 mg/m², oral, every other day. Taper-reduction 10 mg/m² every other day during last 2 weeks of chemotherapy
• Bleomycin
5 u/m² intravenously (IV) on week 2, 4, 6, 8
• Etoposide
60 mg/m² x 2 intravenously (IV) on week 3, 7 (d 15, 16, 43, 44)

Radiation:
• Low-dose radiotherapy (RT)
20 Grey (Gy) modified involved field radiotherapy administered as consolidative irradiation will beginning between 2 and 12 weeks after the completion of Stanford V-C chemotherapy regimen.

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California
United States	Kaiser Permanente Medical Center	Vallejo	California

Sponsors (1)

Lead Sponsor	Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	Progression-free survival was assessed for 3 years from the completion of treatment. Progression-free survival was considered to mean the proportion of patients (percentage) still alive without disease recurrence or progression.	up to 3 years
Secondary	Frequency of Complete Response	The frequency of complete response (CR) is reported as the number (proportion) of subjects in complete response, as assessed during weeks 4 to 5 of chemotherapy. Per protocol, CR is defined as "complete regression of all palpable and radiographic demonstrable disease" by computed tomography (CT) scan or positron emission tomography-CT (PET-CT).	5 weeks
Secondary	Early Treatment-related Toxicity	Early treatment-related toxicity was assessed as the number of treatment-related, non-serious adverse events that occurred during treatment or within 30 days of the completion of treatment.	Within 30 days of treatment
Secondary	Late Treatment-related Toxicity	Late treatment-related toxicity was assessed as the overall number of late-appearing toxicities (ie, related adverse events, after treatment completion) including but not limited to diagnosis of a 2nd cancer; hypothyroidism; infertility; pulmonary toxicity; or cardiac toxicity, at up to 16 years from date of diagnosis.	16 years
Secondary	Second Hodgkin's Disease Progression	Second Hodgkin's disease progression is reported as the number of participants experiencing 2 instances of progression of the underlying Hodgkin's disease, assessed at up to 16 years from date of diagnosis.	16 years
Secondary	Overall Survival (OS)	Overall survival was assessed at up to 16 years from date of diagnosis, and reported as the median years of survival with standard deviation.	16 years
Secondary	Survival at 5 and 10 Years	Survival at 5 and 10 years is expressed at the percentage of subjects known to remain alive at those timepoints.	5 and 10 years