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

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00026208
• Collaborator: (none)
• Enrollment: 76
• Locations: 2
• Arms: 2
• Duration (Months): 188.5
• Patients Per Site: 38
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Hodgkin Disease; Lymphoma; Hodgkin Disease; Lymphoma: Hodgkin	Drug: Vincristine; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Bleomycin; Drug: Etoposide; Radiation: Low-dose radiotherapy (RT)	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients with tumors 5 to 10 cm were to be assigned to concurrent radiotherapy, and participants with tumors less than 5 cm were initially planned to not receive radiotherapy.Patients with tumors 5 to 10 cm were to be assigned to concurrent radiotherapy, and participants with tumors less than 5 cm were initially planned to not receive radiotherapy.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Risk-Adapted Stanford V-C With Radiotherapy for Clinical Stage I and IIA Favorable Hodgkin's Disease: The G5 Study
• Study Start Date: Jun 1, 2001
• Actual Primary Completion Date: Apr 26, 2013
• Actual Study Completion Date: Feb 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stanford V-C + Low-dose Radiotherapy "Sanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. Radiotherapy = 20 Gy modified involved field radiotherapy	Drug: Vincristine; 1.4 mg/m² intravenously (IV) on week 2, 4, 6, 8; Other Names: Vinblastine Leurocristine sulfate Oncovin Vincasar LCR VCR Vincristin Vincristina Vincristinum 22-Oxovincaleukoblastin 22-Oxovincaleukoblastine ; Drug: Cyclophosphamide; 650 mg/m², on week 1 and 5; Other Names: Cytoxan Neosar Cyclophosphamidum Cyclophosphamid Ciclofosfamida Cytophosphane Ledoxina Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester 2-[Bis(2-chloroethylamino)]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide ; Drug: Doxorubicin; 25 mg/m², on week 1, 3, 5, 7; Other Names: Adriamycin Doxorubicinum Doxorubicine Rubex Hydroxydaunomycin HCl Hydroxydoxorubicin HCl Hydroxydaunorubicin 14-hydroxydaunomycin 14-hydroxydaunorubicine (1S,3S)-3-Glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranoside (8S-cis)-10-((3-amino-2,3,6-Trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione ; Drug: Prednisone; 40 mg/m², oral, every other day. Taper-reduction 10 mg/m² every other day during last 2 weeks of chemotherapy; Other Names: Dehydrocortisone Deltasone Liquid Pred Meticorten Orasone Prednicot predniSONE Intensol Rayos Sterapred Prednisona Prednisonum 1,2-Dehydrocortisone 1,4-Pregnadiene-17alpha,21-diol-3,11,20-trione 17,21-Dihydroxypregna-1,4-diene-3,11,20-trione ; Drug: Bleomycin; 5 u/m² intravenously (IV) on week 2, 4, 6, 8; Other Names: Bleomycin A2 Bleomycine Bleocin Bleomicin Bleomicina Bleomycinum BLM ; Drug: Etoposide; 60 mg/m² x 2 intravenously (IV) on week 3, 7 (d 15, 16, 43, 44); Other Names: Toposar Etopophos Vepesid VP-16 Etoposido Etoposidum trans-Etoposide 4-demethylepipodophyllotoxin β-D-ethylideneglucoside 4'-Demethylepipodophyllotoxin 9-(4,6-O-(R)-ethylidene-beta-D-glucopyranoside) 9-((4,6-O-Ethylidine-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,4-dimethyloxyphenyl)furo(3',4'':6,7)naptho-(2,3-d)-1,3-dioxol-6(5aH)-one ; 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.
Experimental: Stanford V-C only "Sanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide.	Drug: Vincristine; 1.4 mg/m² intravenously (IV) on week 2, 4, 6, 8; Other Names: Vinblastine Leurocristine sulfate Oncovin Vincasar LCR VCR Vincristin Vincristina Vincristinum 22-Oxovincaleukoblastin 22-Oxovincaleukoblastine ; Drug: Cyclophosphamide; 650 mg/m², on week 1 and 5; Other Names: Cytoxan Neosar Cyclophosphamidum Cyclophosphamid Ciclofosfamida Cytophosphane Ledoxina Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester 2-[Bis(2-chloroethylamino)]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide ; Drug: Doxorubicin; 25 mg/m², on week 1, 3, 5, 7; Other Names: Adriamycin Doxorubicinum Doxorubicine Rubex Hydroxydaunomycin HCl Hydroxydoxorubicin HCl Hydroxydaunorubicin 14-hydroxydaunomycin 14-hydroxydaunorubicine (1S,3S)-3-Glycoloyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranoside (8S-cis)-10-((3-amino-2,3,6-Trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-5,12-naphthacenedione ; Drug: Prednisone; 40 mg/m², oral, every other day. Taper-reduction 10 mg/m² every other day during last 2 weeks of chemotherapy; Other Names: Dehydrocortisone Deltasone Liquid Pred Meticorten Orasone Prednicot predniSONE Intensol Rayos Sterapred Prednisona Prednisonum 1,2-Dehydrocortisone 1,4-Pregnadiene-17alpha,21-diol-3,11,20-trione 17,21-Dihydroxypregna-1,4-diene-3,11,20-trione ; Drug: Bleomycin; 5 u/m² intravenously (IV) on week 2, 4, 6, 8; Other Names: Bleomycin A2 Bleomycine Bleocin Bleomicin Bleomicina Bleomycinum BLM ; Drug: Etoposide; 60 mg/m² x 2 intravenously (IV) on week 3, 7 (d 15, 16, 43, 44); Other Names: Toposar Etopophos Vepesid VP-16 Etoposido Etoposidum trans-Etoposide 4-demethylepipodophyllotoxin β-D-ethylideneglucoside 4'-Demethylepipodophyllotoxin 9-(4,6-O-(R)-ethylidene-beta-D-glucopyranoside) 9-((4,6-O-Ethylidine-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,4-dimethyloxyphenyl)furo(3',4'':6,7)naptho-(2,3-d)-1,3-dioxol-6(5aH)-one

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [up to 3 years]

   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.

Secondary Outcome Measures

1. Frequency of Complete Response [5 weeks]

   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).

2. Early Treatment-related Toxicity [Within 30 days of treatment]

   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.

3. Late Treatment-related Toxicity [16 years]

   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.

4. Second Hodgkin's Disease Progression [16 years]

   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.

5. Overall Survival (OS) [16 years]

   Overall survival was assessed at up to 16 years from date of diagnosis, and reported as the median years of survival with standard deviation.

6. Survival at 5 and 10 Years [5 and 10 years]

   Survival at 5 and 10 years is expressed at the percentage of subjects known to remain alive at those timepoints.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305
2	Kaiser Permanente Medical Center	Vallejo	California	United States	94589

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Ranjana H Advani, MD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ranjana Advani, Saul A. Rosenberg, MD, Professor of Lymphoma, Stanford University
• ClinicalTrials.gov Identifier: NCT00026208
• Other Study ID Numbers: IRB-13081; LYMHD0002
• First Posted: Jan 27, 2003
• Last Update Posted: Jul 24, 2018
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Lymphoma; Hodgkin Disease; Prednisone; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Etoposide; Etoposide phosphate; Vincristine; Bleomycin; Vinblastine

Study Results

Participant Flow

Arm/Group Title	Stanford V-C + Low-dose Radiotherapy	Stanford V-C Only
Arm/Group Description	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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) "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.	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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)
Period Title: Overall Study
STARTED	72	4
COMPLETED	71	4
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Stanford V-C + Low-dose Radiotherapy	Stanford V-C Only	Total
Arm/Group Description	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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) "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.	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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)	Total of all reporting groups
Overall Participants	72	4	76
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	70 97.2%	4 100%	74 97.4%
>=65 years	2 2.8%	0 0%	2 2.6%
Sex: Female, Male (Count of Participants)
Female	43 59.7%	2 50%	45 59.2%
Male	29 40.3%	2 50%	31 40.8%
Region of Enrollment (participants) [Number]
United States	72 100%	4 100%	76 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	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.
Time Frame	up to 3 years

Outcome Measure Data

Analysis Population Description

Does not include those participants whose treatment was significantly modified due to accidental injury; or who were lost-to-follow-up.

Arm/Group Title	Stanford V-C + Low-dose Radiotherapy	Stanford V-C Only
Arm/Group Description	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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) "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.	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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)
Measure Participants	70	4
Number [percentage of participants]	89.7 124.6%	50 1250%

2. Secondary Outcome

Title	Frequency of Complete Response
Description	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).
Time Frame	5 weeks

Outcome Measure Data

Analysis Population Description

Participants, for whom a PET-CT scan was not conducted in week 4 to 5 of treatment, were not included.

Arm/Group Title	Stanford V-C + Low-dose Radiotherapy	Stanford V-C Only
Arm/Group Description	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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) "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.	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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)
Measure Participants	38	0
Count of Participants [Participants]	31 43.1%

3. Secondary Outcome

Title	Early Treatment-related Toxicity
Description	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.
Time Frame	Within 30 days of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stanford V-C + Low-dose Radiotherapy	Stanford V-C Only
Arm/Group Description	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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) "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.	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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)
Measure Participants	72	4
Number [treatment-related adverse events]	422	24

4. Secondary Outcome

Title	Late Treatment-related Toxicity
Description	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.
Time Frame	16 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stanford V-C + Low-dose Radiotherapy	Stanford V-C Only
Arm/Group Description	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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) "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.	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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)
Measure Participants	72	4
Second Cancer	2	0
Hypothyroidism	19	0

5. Secondary Outcome

Title	Second Hodgkin's Disease Progression
Description	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.
Time Frame	16 years

Outcome Measure Data

Analysis Population Description

Data to confirm Hodgkin's disease 2nd progression was not available for some participants.

Arm/Group Title	Stanford V-C + Low-dose Radiotherapy	Stanford V-C Only
Arm/Group Description	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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) "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.	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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)
Measure Participants	69	4
Count of Participants [Participants]	3 4.2%	1 25%

6. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was assessed at up to 16 years from date of diagnosis, and reported as the median years of survival with standard deviation.
Time Frame	16 years

Outcome Measure Data

Analysis Population Description

Includes all participants, except those whose treatment was significantly modified due to accidental injury. Subjects who became lost-to-follow-up were censored at their last known value.

Arm/Group Title	Stanford V-C + Low-dose Radiotherapy	Stanford V-C Only
Arm/Group Description	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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) "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.	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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)
Measure Participants	71	4
Median (Full Range) [years]	10.4	13.2

7. Secondary Outcome

Title	Survival at 5 and 10 Years
Description	Survival at 5 and 10 years is expressed at the percentage of subjects known to remain alive at those timepoints.
Time Frame	5 and 10 years

Outcome Measure Data

Analysis Population Description

For overall survival at 5 and 10 years, this analysis does not include those participants known to be alive, but whose diagnosis was less than 5 or 10 years prior to current date or last date known alive, respectively.

Arm/Group Title	Stanford V-C + Low-dose Radiotherapy	Stanford V-C Only
Arm/Group Description	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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) "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.	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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)
Measure Participants	69	4
5 years	67 93.1%	3 75%
10 years	41 56.9%	3 75%

Adverse Events

Time Frame	16 years
Arm/Group Title	Stanford V-C + Low-dose Radiotherapy		Stanford V-C Only
Arm/Group Description	"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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) "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.		"Stanford V-C" = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide. 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 mg 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)
All Cause Mortality
	Stanford V-C + Low-dose Radiotherapy		Stanford V-C Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/72 (9.7%)		0/4 (0%)
Serious Adverse Events
	Stanford V-C + Low-dose Radiotherapy		Stanford V-C Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/72 (34.7%)		2/4 (50%)
Cardiac disorders
Atrial fibrillation	1/72 (1.4%)	1	0/4 (0%)	0
Endocrine disorders
Hypothyroidism	17/72 (23.6%)	17	2/4 (50%)	2
General disorders
Fever	5/72 (6.9%)	6	1/4 (25%)	1
Injury, poisoning and procedural complications
Crush injury, automobile accident	1/72 (1.4%)	1	0/4 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Second cancer	2/72 (2.8%)	2	0/4 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/72 (1.4%)	1	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	Stanford V-C + Low-dose Radiotherapy		Stanford V-C Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	72/72 (100%)		4/4 (100%)
Blood and lymphatic system disorders
Infection with grade 3 ANC grade 2 ATT (no hospitalization)	1/72 (1.4%)	1	0/4 (0%)	1
Febrile Neutropenia	1/72 (1.4%)	1	0/4 (0%)	0
Gastrointestinal disorders
Nausea and Vomiting	4/72 (5.6%)	4	0/4 (0%)	0
Metallic Taste in Mouth	1/72 (1.4%)	1	0/4 (0%)	0
Dry Mouth	1/72 (1.4%)	1	0/4 (0%)	0
Oral Mucositis	7/72 (9.7%)	7	0/4 (0%)	0
Mild Oral Sensitivity	1/72 (1.4%)	1	0/4 (0%)	0
Oral Toxicity	8/72 (11.1%)	8	0/4 (0%)	0
Epigastric pain	26/72 (36.1%)	26	1/4 (25%)	1
Nausea	51/72 (70.8%)	51	2/4 (50%)	2
Constipation	40/72 (55.6%)	40	3/4 (75%)	3
Rectal ulcer	0/72 (0%)	0	1/4 (25%)	1
Dysphagia	0/72 (0%)	0	1/4 (25%)	1
Heartburn	1/72 (1.4%)	1	2/4 (50%)	2
Gas pains	1/72 (1.4%)	1	0/4 (0%)	0
Vomiting	18/72 (25%)	18	1/4 (25%)	1
General disorders
Fatigue/Malaise	58/72 (80.6%)	58	3/4 (75%)	3
Fever	3/72 (4.2%)	3	0/4 (0%)	0
Insomnia	27/72 (37.5%)	27	0/4 (0%)	0
Tenderness at the PICC site	1/72 (1.4%)	1	0/4 (0%)	0
Discomfort, burning & increased sensitivity	1/72 (1.4%)	1	0/4 (0%)	0
PICC line removed	1/72 (1.4%)	1	0/4 (0%)	0
Chest soreness and tightness	1/72 (1.4%)	1	0/4 (0%)	0
Pain, inflammation of left arm above IV site	1/72 (1.4%)	1	0/4 (0%)	0
Aches and pains	1/72 (1.4%)	1	0/4 (0%)	0
Pain, axilla & breast	0/72 (0%)	0	1/4 (25%)	1
Sorness in upper and lower extremities	1/72 (1.4%)	1	0/4 (0%)	0
Substernal chest pressure	1/72 (1.4%)	1	0/4 (0%)	0
Pain, abdominal	1/72 (1.4%)	1	0/4 (0%)	0
Pain, jaw	2/72 (2.8%)	2	0/4 (0%)	0
Pain, hips and legs	1/72 (1.4%)	1	0/4 (0%)	0
Joint pains, back and hips	1/72 (1.4%)	1	0/4 (0%)	0
Ache and heaviness in left arm	1/72 (1.4%)	1	0/4 (0%)	0
Pain, right groin	1/72 (1.4%)	1	0/4 (0%)	0
Pain	3/72 (4.2%)	3	0/4 (0%)	0
Generalized achiness	2/72 (2.8%)	2	0/4 (0%)	0
Flu-like symptoms	1/72 (1.4%)	1	0/4 (0%)	0
Pain, related to PICC	1/72 (1.4%)	1	0/4 (0%)	0
Weight loss	1/72 (1.4%)	1	0/4 (0%)	0
Chills	1/72 (1.4%)	1	0/4 (0%)	0
Infections and infestations
Fungal rash	1/72 (1.4%)	1	0/4 (0%)	0
Infection	1/72 (1.4%)	1	0/4 (0%)	0
Investigations
Lymphocyte count decreased	55/72 (76.4%)	101	4/4 (100%)	11
Neutrophil count decreased	2/72 (2.8%)	2	0/4 (0%)	0
Neutrophil count decreased	41/72 (56.9%)	48	2/4 (50%)	3
Metabolism and nutrition disorders
Alanine aminotransferase increased	1/72 (1.4%)	1	0/4 (0%)	0
Anorexia	1/72 (1.4%)	1	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
Bone pain	5/72 (6.9%)	5	0/4 (0%)	0
Pain, bilateral arms	1/72 (1.4%)	1	0/4 (0%)	0
Myalgias	3/72 (4.2%)	3	0/4 (0%)	0
Pain, bone and muscle	4/72 (5.6%)	4	0/4 (0%)	0
Muscle aches	1/72 (1.4%)	1	0/4 (0%)	0
Pain, lower back	1/72 (1.4%)	1	0/4 (0%)	0
Arthralgias	1/72 (1.4%)	1	0/4 (0%)	0
Nervous system disorders
Peripheral Sensory Neuropathy	40/72 (55.6%)	40	3/4 (75%)	3
Peripheral Motor Neuropathy	2/72 (2.8%)	2	0/4 (0%)	0
Syncopal episode with brief loss of consciousness	1/72 (1.4%)	1	0/4 (0%)	0
Altered taste sensation	1/72 (1.4%)	1	0/4 (0%)	0
Headache	4/72 (5.6%)	4	1/4 (25%)	1
Dizziness	1/72 (1.4%)	1	0/4 (0%)	0
Headache	1/72 (1.4%)	1	1/4 (25%)	1
Psychiatric disorders
Depression	1/72 (1.4%)	1	0/4 (0%)	0
Anxiety	3/72 (4.2%)	3	0/4 (0%)	0
Mood Alteration	1/72 (1.4%)	1	0/4 (0%)	0
Renal and urinary disorders
Blood spotting	1/72 (1.4%)	1	0/4 (0%)	0
Gross hematuria	1/72 (1.4%)	1	0/4 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pneumonia	1/72 (1.4%)	1	0/4 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	2/72 (2.8%)	2	0/4 (0%)	0
Diaphoresis	1/72 (1.4%)	1	0/4 (0%)	0
Skin toxicity	2/72 (2.8%)	2	0/4 (0%)	0
Rash	1/72 (1.4%)	1	0/4 (0%)	0
Swelling	1/72 (1.4%)	1	0/4 (0%)	0
Vascular disorders
Acute Pulmonary Embolism	1/72 (1.4%)	1	0/4 (0%)	0
Vein Pain	6/72 (8.3%)	6	1/4 (25%)	1
Phlebitis	1/72 (1.4%)	1	0/4 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.