Therapy for Pediatric Hodgkin Lymphoma

Study Overview
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Brief Summary
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With the success of current chemotherapy for Hodgkin's disease, the goal of this protocol is to maintain the currently successful cure rate and reduce treatment related side effects and long term toxicity. The main purpose of this study is to estimate the event free survival of patients treated with risk-adapted therapy compared to historical controls.

Detailed Description
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This study will evaluate the following objectives: Primary Objectives: To evaluate the efficacy of 4 cycles of VAMP chemotherapy alone in patients with favorable risk Hodgkin's disease who achieve a complete response after 2 cycles of VAMP chemotherapy. To evaluate the efficacy of 4 cycles VAMP chemotherapy plus low dose RT in patients with favorable risk Hodgkin's disease who achieve a partial response after 2 cycles of VAMP chemotherapy. To evaluate the efficacy of 2 alternating cycles of VAMP/COP chemotherapy (total 4 cycles of chemotherapy) plus low-dose, involved-field RT in children with intermediate risk Hodgkin's disease. To evaluate the efficacy of 12 weeks of Stanford V chemotherapy plus low-dose, involved-field RT in children with unfavorable risk Hodgkin's disease. Secondary Objectives: To evaluate patient quality of life during and after treatment from the patient and parent perspective. To compare patient and parental ratings of treatment-related symptoms and patient physical, psychological, social and cognitive functioning before the first treatment (T1 - baseline); after Cycle 2 or after 8 weeks of Stanford V (T2 - Evaluate Response); after cycle 4 or after 12 weeks of Stanford V and before or on the first day of radiation (as applicable) (T3); at the conclusion of radiation or within a few days following the end of radiation (as applicable) (T4); and at 3 to 6 months after completion of therapy follow-up evaluation (T5).

Official Title
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Risk-Adapted Therapy for Pediatric Hodgkin's Disease

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Drug: 12 Week Stanford V Chemotherapy
* Drug: 4 cycles of VAMP chemotherapy
* Drug: 2 alternating cycles of VAMP/COP chemotherapy
* Drug: 3 alternating cycles of VAMP/COP chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible patients must have histologically confirmed previously untreated Hodgkin's disease (Patients receiving limited emergent RT or steroid therapy because of cardiopulmonary decompensation or spinal cord compression will be eligible for protocol enrollment). Patients must be 21 years of age or younger Ann Arbor stages IIB-IV No prior treatment. No pregnant or lactating women. Signed informed consent If re-evaluation of a patient's disease shows favorable risk features or intermediate risk features, the patient will be removed from the HOD99 study and consented to the respective HOD08 or HOD05 study. Inclusion: treatment of favorable risk features: Ann Arbor IA or IIA with: Non-bulky mediastinal disease (<33% mediastinal to thoracic ratio on chest x ray) Ann Arbor stage IA or IIA with any of the following features: (1) E lesions (s), (2) 3 or more nodal sites involved, (3) Bulky mediastinal adenopathy (mediastinal mass to thoracic cavity ratio 33% or greater by chest radiograph) Inclusion: unfavorable risk features: Stage must be classified as one of the following: Ann Arbor stage IIB, IIIB, or any IV

Ages Eligible for Study
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Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Unfavorable Risk, Group 2<br>Unfavorable risk, group 2 arm in patients with Hodgkin's disease (n=146) | Drug: 12 Week Stanford V Chemotherapy<br>* 12 weeks of Stanford V chemotherapy plus low-dose, involved-field RT in children<br>|
| Experimental: Favorable Risk<br>Favorable Risk arm in patients with Hodgkin's Disease (n=91). | Drug: 4 cycles of VAMP chemotherapy<br>* 4 cycles of VAMP chemotherapy alone in patients who achieve a complete response after 2 cycles of VAMP chemotherapy. For patients that do not achieve a complete response after 2 cycles of VAMP, they will receive low low-dose involved field radiotherapy at the end of all chemotherapy.<br>|
| Experimental: Intermediate Risk<br>Intermediate Arm in patients with Hodgkins's disease (n=46). | Drug: 2 alternating cycles of VAMP/COP chemotherapy<br>* 2 alternating cycles of VAMP/COP chemotherapy (total 4 cycles of chemotherapy) plus low-dose, involved-field RT.<br>|
| Experimental: Unfavorable Risk, Group 1<br>Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13). | Drug: 3 alternating cycles of VAMP/COP chemotherapy<br>* 3 alternating cycles of VAMP/COP chemotherapy (total 6 cycles of chemotherapy) plus low-dose, involved-field RT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free Survival Probability by Risk Group | Event-free survival (EFS) is based on the time from protocol enrollment to the occurrence of first event (relapse or progressive disease, subsequent malignancy, or death from any cause). Patients not experiencing an event are censored at their last follow-up date. Event-free Survival Probability will be estimated by Kaplan-Meier (KM) method with a 95% confidence interval calculated using the Greenwood's formula. | Median 6.4 year follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of Agreement Between Patient Physical QoL and Parent Proxy Physical QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy physical quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5). | 
| Correlation of Agreement Between Patient Emotional QoL and Parent Proxy Emotional QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy emotional quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5). | 
| Correlation of Agreement Between Patient Social QoL and Parent Proxy Social QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy social quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5). | 
| Correlation of Agreement Between Patient School QoL and Parent Proxy School QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy school quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5). | 
| Correlation of Agreement Between Patient Psychosocial QoL and Parent Proxy Psychosocial QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy psychosocial quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5). | 
| Correlation of Agreement Between Patient Peds QL4 (Composite) QoL and Parent Proxy Peds QL4 (Composite) QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy Peds QL4 (composite) quality of life across multiple time points using the Peds Quality of Life version 4. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5). | 
| Correlation of Agreement Between Patient Pain and Hurt QoL and Parent Proxy Pain and Hurt QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy pain and hurt quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5). | 
| Correlation of Agreement Between Patient Nausea QoL and Parent Proxy Nausea QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy nausea quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5) | 
| Correlation of Agreement Between Patient Procedural Anxiety QoL and Parent Proxy Procedural Anxiety QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy procedural anxiety quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5) | 
| Correlation of Agreement Between Patient Treatment Anxiety QoL and Parent Proxy Treatment Anxiety QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy treatment anxiety quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5) | 
| Correlation of Agreement Between Patient Worry QoL and Parent Proxy Worry QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy worry quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5) | 
| Correlation of Agreement Between Patient Cognitive Problems (Child + Teen) QoL and Parent Proxy Cognitive Problems (Child + Teen) QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy cognitive problems (child + teen) quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5) | 
| Correlation of Agreement Between Patient Perceived Physical Appearance QoL and Parent Proxy Perceived Physical Appearance QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy perceived physical appearance quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5) | 
| Correlation of Agreement Between Patient Communication QoL and Parent Proxy Communication QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy communication quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5) | 
| Correlation of Agreement Between Patient PedsQL3 (Composite) QoL and Parent Proxy PedsQL3 (Composite) QoL at Multiple Time Points. | Assess and compare the patient reported and parent proxy PedsQL3 (composite) quality of life across multiple time points using the Peds Quality of Life version 3. Assessment was performed across all risk groups. The QL scoring is a 5-point Likert scale from 0 (never) to 4 (almost always). Scores are transformed on a scale from 0 to 100. Items are reverse scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, and 4=0. Total score is the sum of all items over the number of items answered on all scales. The higher the score, the better the quality of life. | At completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), and 3-6 months after the completion of therapy (T5) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Hodgkin Disease