Trial Outcomes & Findings for Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma (NCT NCT00302003)
NCT ID: NCT00302003
Last Updated: 2021-03-30
Results Overview
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).
COMPLETED
PHASE3
287 participants
At 60 months
2021-03-30
Participant Flow
Participant milestones
| Measure |
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.
radiation therapy: Undergo radiation therapy
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
filgrastim: Given IV or subcutaneously
|
|---|---|
|
Overall Study
STARTED
|
287
|
|
Overall Study
COMPLETED
|
207
|
|
Overall Study
NOT COMPLETED
|
80
|
Reasons for withdrawal
| Measure |
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.
radiation therapy: Undergo radiation therapy
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
filgrastim: Given IV or subcutaneously
|
|---|---|
|
Overall Study
Lack of Efficacy
|
62
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Physician Decision
|
2
|
|
Overall Study
Withdrawal by Subject
|
5
|
|
Overall Study
Ineligible
|
9
|
|
Overall Study
Protocol Violation
|
1
|
Baseline Characteristics
Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma
Baseline characteristics by cohort
| Measure |
Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim
n=287 Participants
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.
radiation therapy: Undergo radiation therapy
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
filgrastim: Given IV or subcutaneously
|
|---|---|
|
Age, Categorical
<=18 years
|
272 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Age, Continuous
|
15 Years
n=99 Participants
|
|
Sex: Female, Male
Female
|
160 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
127 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
43 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
227 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
17 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
3 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
8 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
29 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
220 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
27 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
250 participants
n=99 Participants
|
|
Region of Enrollment
Australia
|
3 participants
n=99 Participants
|
|
Region of Enrollment
Canada
|
25 participants
n=99 Participants
|
|
Region of Enrollment
Israel
|
1 participants
n=99 Participants
|
|
Region of Enrollment
Mexico
|
1 participants
n=99 Participants
|
|
Region of Enrollment
New Zealand
|
2 participants
n=99 Participants
|
|
Region of Enrollment
Puerto Rico
|
4 participants
n=99 Participants
|
|
Region of Enrollment
Switzerland
|
1 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: At 60 monthsPopulation: Eligible (n=278) and evaluable response and review of response, n=275. Follow-up for censored patients (n=138) is 76 months (range: 1.8 to 108 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).
Outcome measures
| Measure |
Group 1
n=275 Participants
Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim
|
|---|---|
|
Event Free Survival Without Receiving Radiation Therapy (EFSnoRT).
|
0.49 Probability of survival
Interval 0.42 to 0.54
|
PRIMARY outcome
Timeframe: At 60 monthsPopulation: Eligible (n=278) and evaluable response and review of response, n=275. Follow-up for censored patients (n=245) is 76 months (range: 4.7 to 109 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.
Outcome measures
| Measure |
Group 1
n=275 Participants
Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim
|
|---|---|
|
Intensive Therapy Free Survival (ITFS).
|
0.89 Probability of survival
Interval 0.84 to 0.92
|
PRIMARY outcome
Timeframe: At 60 monthsPopulation: Eligible (n=278). Follow-up for censored patients (n=223) is 75 months (range: 4.7 to 108 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).
Outcome measures
| Measure |
Group 1
n=278 Participants
Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim
|
|---|---|
|
Event Free Survival (EFS)
|
0.79 Probability of survival
Interval 0.74 to 0.84
|
SECONDARY outcome
Timeframe: At 60 monthsPopulation: Eligible (n=278). Follow-up for censored patients (n=277) is 76 months (range: 4.7 to 109 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.
Outcome measures
| Measure |
Group 1
n=278 Participants
Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim
|
|---|---|
|
Overall Survival
|
0.99 Probability of survival
Interval 0.97 to 1.0
|
Adverse Events
Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim
Serious adverse events
| Measure |
Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim
n=278 participants at risk
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.
radiation therapy: Undergo radiation therapy
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
filgrastim: Given IV or subcutaneously
|
|---|---|
|
Infections and infestations
Infections and infestations - Other, specify
|
0.36%
1/278 • Number of events 1
|
|
Investigations
CPK increased
|
0.36%
1/278 • Number of events 1
|
|
Metabolism and nutrition disorders
Acidosis
|
0.36%
1/278 • Number of events 1
|
|
Vascular disorders
Thromboembolic event
|
0.36%
1/278 • Number of events 1
|
Other adverse events
| Measure |
Doxorubicin, Vincristine, Cyclophosphamide and Filgrastim
n=278 participants at risk
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.
radiation therapy: Undergo radiation therapy
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
filgrastim: Given IV or subcutaneously
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
6.5%
18/278 • Number of events 18
|
|
Ear and labyrinth disorders
Hearing impaired
|
0.72%
2/278 • Number of events 2
|
|
Ear and labyrinth disorders
Tinnitus
|
0.72%
2/278 • Number of events 2
|
|
Endocrine disorders
Delayed puberty
|
0.36%
1/278 • Number of events 1
|
|
Endocrine disorders
Hypothyroidism
|
0.36%
1/278 • Number of events 1
|
|
Eye disorders
Eye pain
|
0.36%
1/278 • Number of events 1
|
|
Eye disorders
Optic nerve disorder
|
0.36%
1/278 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
1.1%
3/278 • Number of events 3
|
|
Gastrointestinal disorders
Constipation
|
1.1%
3/278 • Number of events 3
|
|
Gastrointestinal disorders
Enterocolitis
|
0.36%
1/278 • Number of events 1
|
|
Gastrointestinal disorders
Esophageal pain
|
0.36%
1/278 • Number of events 1
|
|
Gastrointestinal disorders
Esophagitis
|
0.36%
1/278 • Number of events 1
|
|
Gastrointestinal disorders
Ileus
|
0.72%
2/278 • Number of events 2
|
|
Gastrointestinal disorders
Mucositis oral
|
1.4%
4/278 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
3.6%
10/278 • Number of events 10
|
|
Gastrointestinal disorders
Oral pain
|
0.72%
2/278 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
3.6%
10/278 • Number of events 10
|
|
General disorders
Fatigue
|
1.4%
4/278 • Number of events 4
|
|
General disorders
Pain
|
0.72%
2/278 • Number of events 2
|
|
Immune system disorders
Anaphylaxis
|
0.36%
1/278 • Number of events 1
|
|
Infections and infestations
Bladder infection
|
0.36%
1/278 • Number of events 1
|
|
Infections and infestations
Catheter related infection
|
0.72%
2/278 • Number of events 2
|
|
Infections and infestations
Infections and infestations - Other, specify
|
4.3%
12/278 • Number of events 12
|
|
Infections and infestations
Lung infection
|
0.36%
1/278 • Number of events 1
|
|
Infections and infestations
Skin infection
|
0.36%
1/278 • Number of events 1
|
|
Infections and infestations
Soft tissue infection
|
0.36%
1/278 • Number of events 1
|
|
Infections and infestations
Tracheitis
|
0.36%
1/278 • Number of events 1
|
|
Infections and infestations
Upper respiratory infection
|
0.72%
2/278 • Number of events 2
|
|
Injury, poisoning and procedural complications
Vascular access complication
|
1.4%
4/278 • Number of events 4
|
|
Investigations
Alanine aminotransferase increased
|
0.72%
2/278 • Number of events 2
|
|
Investigations
Aspartate aminotransferase increased
|
0.72%
2/278 • Number of events 2
|
|
Investigations
Lymphocyte count decreased
|
0.36%
1/278 • Number of events 1
|
|
Investigations
Neutrophil count decreased
|
2.5%
7/278 • Number of events 7
|
|
Investigations
Platelet count decreased
|
0.36%
1/278 • Number of events 1
|
|
Investigations
White blood cell decreased
|
2.2%
6/278 • Number of events 6
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
1.1%
3/278 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.36%
1/278 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
0.36%
1/278 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypokalemia
|
2.5%
7/278 • Number of events 7
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.36%
1/278 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
1.1%
3/278 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.36%
1/278 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.72%
2/278 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
0.36%
1/278 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
1.1%
3/278 • Number of events 3
|
|
Nervous system disorders
Headache
|
1.1%
3/278 • Number of events 3
|
|
Nervous system disorders
Neuralgia
|
1.4%
4/278 • Number of events 4
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.72%
2/278 • Number of events 2
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.36%
1/278 • Number of events 1
|
|
Nervous system disorders
Syncope
|
0.72%
2/278 • Number of events 2
|
|
Nervous system disorders
Vasovagal reaction
|
0.36%
1/278 • Number of events 1
|
|
Psychiatric disorders
Agitation
|
0.36%
1/278 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
0.36%
1/278 • Number of events 1
|
|
Psychiatric disorders
Depression
|
0.36%
1/278 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
0.72%
2/278 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.36%
1/278 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal mucositis
|
0.36%
1/278 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
0.36%
1/278 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.36%
1/278 • Number of events 1
|
|
Vascular disorders
Hypotension
|
0.72%
2/278 • Number of events 2
|
|
Vascular disorders
Thromboembolic event
|
0.72%
2/278 • Number of events 2
|
Additional Information
Results Reporting Coordinator
Children's Oncology Group
Results disclosure agreements
- Principal investigator is a sponsor employee Must obtain prior Sponsor approval.
- Publication restrictions are in place
Restriction type: OTHER