IIB期、IIIB期およびIV期ホジキンリンパ腫の若年患者の治療におけるアドセトリス（ブレンツキシマブ ベドチン）、併用化学療法、および放射線療法
Adcetris (ブレンツキシマブ ベドチン)、OEPA/COPDac レジメン [Euro-Net C1 の治療グループ 3 (TG3)] におけるビンクリスチンの代替
This pilot phase II trial studies how well giving brentuximab vedotin, combination chemotherapy, and radiation therapy works in treating younger patients with stage IIB, IIIB or IV Hodgkin lymphoma. Monoclonal antibodies, such as brentuximab vedotin, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer killing substances to them. Drugs used in chemotherapy, such as etoposide, prednisone, doxorubicin hydrochloride, cyclophosphamide, and dacarbazine, 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 brentuximab vedotin with combination chemotherapy may kill more cancer cells and reduce the need for radiation therapy.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
PRIMARY OBJECTIVES:
- To evaluate the safety of brentuximab vedotin, etoposide, prednisone and doxorubicin hydrochloride (AEPA)/cyclophosphamide, brentuximab vedotin, prednisone and dacarbazine (CAPDac), as well as the efficacy (early complete response) after 2 cycles of AEPA chemotherapy in high risk patients with Hodgkin lymphoma (HL).
- To compare the event-free survival in high risk HL patients treated with AEPA/CAPDac to the historical control unfavorable risk 2 arm (UR2) of the St. Jude HOD99 study.
SECONDARY OBJECTIVES:
- To estimate the number of patients with adequate response according to the definitions in the Euro-Net C1 after 2 cycles of AEPA.
- To evaluate the safety of Adcetris (brentuximab vedotin) in the AEPA/CAPDac regimen in children with high risk HL.
- To describe acute hematologic, neuropathic, and infectious toxicities as they relate to transfusion requirements, growth factor support, episodes of febrile neutropenia and hospitalizations, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.
- To study the association between local failure and original lymph node region and volume of radiation (patterns of treatment failure).
- To assess patient-reported symptoms and health-related quality of life in children with high risk HL compared to those treated on the unfavorable treatment arm of the St. Jude HOD99 study.
OUTLINE:
AEPA REGIMEN: Patients receive brentuximab vedotin on days 1, 8, and 15, etoposide on days 1 to 5, prednisone three times daily (TID) on days 1 to 15, and doxorubicin hydrochloride on days 1 and 15. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
CAPDac REGIMEN: Patients receive cyclophosphamide on days 1 and 8, brentuximab vedotin days 1 and 8, prednisone TID on days 1 to 15, and dacarbazine on days 1 to 3. Treatment repeats every 21-28 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Beginning 2-3 weeks after CAPDac chemotherapy, patients with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy undergo radiation therapy daily, 5 days a week for 3-4 weeks.
After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually for 5 years.
研究の種類
研究の種類
入学 (実際)
入学
段階
段階
- フェーズ2
連絡先と場所
研究場所
-
-
California
-
Palo Alto、California、アメリカ、94304
- Lucile Packard Children's Hospital Stanford University
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Illinois
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Peoria、Illinois、アメリカ、61637
- St. Jude Midwest Affiliate
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Maine
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Scarborough、Maine、アメリカ、04704
- Maine Children's Cancer Program (MCCP)
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-
Massachusetts
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Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital Cancer Center
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Boston、Massachusetts、アメリカ、02115
- Dana-Farber Harvard Cancer Center
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Tennessee
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Memphis、Tennessee、アメリカ、38105
- St. Jude Children's Research Hospital
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-
参加基準
適格基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Histologically confirmed, previously untreated CD30+ classical Hodgkin Lymphoma (HL). (Participants receiving limited emergent radiation therapy (RT) or steroid therapy - maximum of 7 days - because of cardiopulmonary decompensation or spinal cord compression will be eligible for protocol enrollment).
- Age ≤ 18 years at the time of diagnosis (i.e., participants are eligible until their 19th birthday).
- Ann Arbor stage IIB, IIIB, IVA, or IVB.
- Adequate renal function based on GFR ≥ 70 ml/min/1.73m^2 or serum creatinine adjusted for age and gender.
- Adequate hepatic function (total bilirubin < 1.5 x ULN for age, and SGOT/SGPT < 2.5 x ULN for age).
- Female participant who is post-menarchal must have a negative urine or serum pregnancy test.
- Female or male participant of reproductive potential must agree to use an effective contraceptive method throughout duration of study treatment.
Exclusion Criteria:
- CD30 negative HL.
- Has received prior therapy for Hodgkin lymphoma, except as noted above.
- Inadequate organ function as described above.
- Inability or unwillingness of research participant or legal guardian / representative to give written informed consent.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
実験的：Treatment
Participants receive AEPA regimen (brentuximab vedotin, etoposide, prednisone, doxorubicin), and CAPDac regimen (cyclophosphamide, brentuximab vedotin, prednisone, dacarbazine(R)). Filgrastim may be given as clinically indicated. For those with lymph nodes that do not go into remission after 2 courses of AEPA chemotherapy, radiation therapy will be given. Some participants may volunteer to complete the quality of life assessment. |
Given intravenously (IV).
他の名前：
Given IV.
他の名前：
Given orally (PO).
他の名前：
Given IV.
他の名前：
Given IV.
他の名前：
Given IV.
他の名前：
Given subcutaneously (SQ) as clinically indicated.
他の名前：
Quality of life assessment will be done at initial clinical visit, and during chemotherapy, completion of therapy, then at 1 year, 2 years and 5 years. It should take no more than 15-20 minutes to complete. Participation is voluntary by participating institution and by participant. At the end of chemotherapy and recovery of blood counts, radiotherapy will be given to any involved nodes (if any) that are not in complete remission.
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Percentage of Initially Enrolled Patients That Have a Complete Response at Early Response Assessment Compared to Historical Control
時間枠：After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)
|
To determine the efficacy of 2 cycles of AEPA chemotherapy, the response rate for the first 32 evaluable participants enrolled was evaluated. If it shown efficacy (detect 20% increase complete rate with 80% power and 5% type I error compared with the proportion of historical control of HOD99 (NCT00145600) unfavorable risk patients had complete rate at week 8 of 17% (24/141), the response results will be reported in a national/international meeting and the study will continue to enroll for a total of 77 patients. |
After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)
|
|
Percentage of Initially Enrolled Patients That Have a Complete Response at Early Response Assessment Compared to Historical Control
時間枠：After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)
|
To determine the efficacy of 2 cycles of AEPA chemotherapy, the response rate for the first 32 evaluable participants enrolled was evaluated. If it shown efficacy (detect 20% increase complete rate with 80% power and 5% type I error compared with the proportion of historical control of HOD99 unfavorable risk patients had complete rate at week 8 of 17% (24/141), the response results will be reported in a national/international meeting and the study will continue to enroll for a total of 77 patients. |
After the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)
|
|
Complete Response Rate Estimate for All Evaluable Participants
時間枠：After the first 2 cycles of chemotherapy (at 2 months from enrollment for each participant)
|
To evaluate the safety of AEPA/CAPDac, as well as the efficacy (early complete response) after 2 cycles of AEPA chemotherapy in high-risk patients with Hodgkin Lymphoma (HL). |
After the first 2 cycles of chemotherapy (at 2 months from enrollment for each participant)
|
|
Comparison of the Event-free (EFS) Survival in High Risk HL Patients Treated With AEPA/CAPDac to the Historical Control HOD99 Unfavorable Risk 2 Arm (UR2).
時間枠：From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment)
|
Event-free survival (EFS) is defined as the probability of survival between the date of study enrollment to the date of first event (relapsed or progressive disease, second malignancy, or death from any cause) or to last follow-up for patients without events. Under the proportional hazard model assumption, the two-sample log-rank test used to compare the EFS between HLHR13 and historical control of HOD99 unfavorable risk 2 arm (UR2). |
From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment)
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Local Failure Rate in High Risk HL Patients Treated With AEPA/CAPDac.
時間枠：From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment)
|
The local failure rate within the high-risk HL participants treated with AEPA/CAPDac will be estimated with a 95% confidence interval using appropriate methods (e.g., estimate cumulative incidence in the presence of competing risks). |
From start of therapy to 2 years after completion of therapy (up to 3 years after study enrollment)
|
|
Descriptive of Hematological Adverse Events
時間枠：From enrollment to end of therapy (approximately 8 months)
|
To describe acute hematologic, neuropathic, and infectious toxicities as they relate to transfusion requirements, growth factor support, episodes of febrile neutropenia and hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. |
From enrollment to end of therapy (approximately 8 months)
|
|
Descriptive of Infectious Adverse Events
時間枠：From enrollment to end of therapy (approximately 8 months)
|
To describe acute hematologic, neuropathic, and infectious toxicities as they relate to transfusion requirements, growth factor support, episodes of febrile neutropenia and hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. |
From enrollment to end of therapy (approximately 8 months)
|
|
Descriptive of Neuropathic Adverse Events
時間枠：From enrollment to end of therapy (approximately 8 months)
|
To describe acute hematologic, neuropathic, and infectious toxicities as they relate to transfusion requirements, growth factor support, episodes of febrile neutropenia and hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. |
From enrollment to end of therapy (approximately 8 months)
|
|
To Assess the Patient Reported Symptoms and Health-related Quality of Life in Children With High Risk HL Compared to Those Treated on the Unfavorable HOD99 Treatment Arm (UR2) at Multiple Time Points. (PedsQL v.3.0)
時間枠：At Diagnosis (baseline) (T1), completion of 2 cycles of chemotherapy (approximately 2 months) (T2), completion of 4 cycles of chemotherapy (approximately 4 months) (T3), completion of radiation (approximately 8 months) (T4)
|
Assess and compare the patient reported quality of life and symptom distress to that of patients treated on the HOD99 unfavorable risk 2 arm (UR2) using the Peds Quality of Life version 3. 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. For both the total score and subscales the range is 0-100. The total score is the sum of all items from each subscale, over the number of items answered on the scale. The total score is the sum of all items on the scale over the number of items answer. If >50% of the items are missing the score should not be computed. If >50% are completed, impute the mean of the completed items in a scale. The Higher the score the better quality of life. |
At Diagnosis (baseline) (T1), completion of 2 cycles of chemotherapy (approximately 2 months) (T2), completion of 4 cycles of chemotherapy (approximately 4 months) (T3), completion of radiation (approximately 8 months) (T4)
|
|
To Assess the Patient Reported Symptoms and Health-related Quality of Life in Children With High Risk HL Compared to Those Treated on the Unfavorable HOD99 Treatment Arm (UR2) at Multiple Time Points. (PedsQL v.4.0)
時間枠：At Diagnosis (baseline) (T1), completion of 2 cycles of chemotherapy (approximately 2 months) (T2), completion of 4 cycles of chemotherapy (approximately 4 months) (T3), completion of radiation (approximately 8 months) (T4)
|
Assess and compare the patient reported quality of life and symptom distress to that of patients treated on the HOD99 unfavorable risk 2 arm (UR2) using the Peds Quality of Life version 4. 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. For both the total score and subscales the range is 0-100. The total score is the sum of all items from each subscale, over the number of items answered on the scale. The total score is the sum of all items on the scale over the number of items answer. If >50% of the items are missing the score should not be computed. If >50% are completed, impute the mean of the completed items in a scale. The Higher the score the better quality of life. |
At Diagnosis (baseline) (T1), completion of 2 cycles of chemotherapy (approximately 2 months) (T2), completion of 4 cycles of chemotherapy (approximately 4 months) (T3), completion of radiation (approximately 8 months) (T4)
|
|
Response Rate
時間枠：after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)
|
Response compared to the Euro-Net C1 after 2 cycles of AEPA. |
after the first 2 cycles of chemotherapy (at approximately 2 months after enrollment)
|
|
Patient Quality of Life (QoL)
時間枠：At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment).
|
Patient QOL will be measured at multiple time points to assess the patient's physical emotional, social, and school functioning. 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. For both the total score and subscales the range is 0-100. The total score is the sum of all items from each subscale, over the number of items answered on the scale. The total score is the sum of all items on the scale over the number of items answer. If >50% of the items are missing the score should not be computed. If >50% are completed, impute the mean of the completed items in a scale. The Higher the score the better quality of life. |
At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment).
|
|
Parent Proxy Quality of Life (QoL)
時間枠：At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment)
|
Parent's assessment of child's physical, emotional, social and school functioning over multiple time points. 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. For both the total score and subscales the range is 0-100. The total score is the sum of all items from each subscale, over the number of items answered on the scale. The total score is the sum of all items on the scale over the number of items answer. If >50% of the items are missing the score should not be computed. If >50% are completed, impute the mean of the completed items in a scale. The Higher the score the better quality of life. |
At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment)
|
|
Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points
時間枠：At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment)
|
The correlation of agreement between patient and parent Quality of Life is calculated by using the Pearson's Correlation Coefficient, which considers only the record with both parent and patient data. 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. For both the total score and subscales the range is 0-100. The total score is the sum of all items from each subscale, over the number of items answered on the scale. The total score is the sum of all items on the scale over the number of items answer. If >50% of the items are missing the score should not be computed. If >50% are completed, impute the mean of the completed items in a scale. The Higher the score the better quality of life. |
At various time points from diagnosis through 5 years off therapy. (up to approximately 6 years from enrollment)
|
協力者と研究者
捜査官
捜査官
- 主任研究者：Matt Ehrhardt, MD、St. Jude Children's Research Hospital
出版物と役立つリンク
一般刊行物
- Metzger ML, Link MP, Billett AL, Flerlage J, Lucas JT Jr, Mandrell BN, Ehrhardt MJ, Bhakta N, Yock TI, Friedmann AM, de Alarcon P, Luna-Fineman S, Larsen E, Kaste SC, Shulkin B, Lu Z, Li C, Hiniker SM, Donaldson SS, Hudson MM, Krasin MJ. Excellent Outcome for Pediatric Patients With High-Risk Hodgkin Lymphoma Treated With Brentuximab Vedotin and Risk-Adapted Residual Node Radiation. J Clin Oncol. 2021 Jul 10;39(20):2276-2283. doi: 10.1200/JCO.20.03286. Epub 2021 Apr 7.
- Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28.
研究記録日
主要日程の研究
研究開始 (実際)
研究開始
一次修了 (実際)
一次修了
研究の完了 (推定)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (推定)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
- 免疫系疾患
- 組織型別の新生物
- リンパ疾患
- リンパ増殖性疾患
- 免疫増殖性疾患
- リンパ腫
- ヘミックおよびリンパ疾患
- 新生物
- ホジキン病
- ペプチド
- アミノ酸、ペプチド、およびタンパク質
- オリゴペプチド
- タンパク質
- 有機化学物質
- 複素環化化合物、1リング
- 複素環化化合物
- 治療
- アゾール
- 炭化水素
- 炭化水素、周期的
- 生物学的要因
- 炭水化物
- 物理現象
- ポドフィロトキシン
- テトラヒドロノフタレン
- ナフタレン
- 多環芳香族炭化水素
- 炭化水素、芳香
- 多環式化合物
- グルコシド
- グリコシド
- トリアゼン
- イミダゾール
- 抗体、モノクローナル、ヒト化
- 抗体、モノクローナル
- 抗体
- 免疫グロブリン
- 免疫タンパク質
- 血液タンパク質
- 血清グロブリン
- グロブリン
- 妊娠
- 妊娠
- ステロイド
- 融合リング化合物
- ホスホルアミドマスタード
- 窒素マスタード化合物
- マスタード化合物
- 炭化水素、ハロゲン化
- ホスホラミド
- 有機リン化合物
- 細胞間シグナル伝達ペプチドとタンパク質
- 妊娠症
- 妊娠した
- アントラサイクリン
- ナフテセン
- アミノグリコシド
- 糖タンパク質
- グリココンジュゲート
- ダウノルビシン
- コロニー刺激因子
- 造血細胞成長因子
- サイトカイン
- 顆粒球コロニー刺激因子
- ブレンツキシマブ ベドチン
- プレドニン
- プレドニゾロン
- シクロホスファミド
- エトポシド
- ドキソルビシン
- ダカルバジン
- 放射線療法
- 放射線
- Filgrastim
その他の研究ID番号
その他の研究ID番号
- HLHR13
- NCI-2013-01123 (レジストリ識別子：NCI Clinical Trial Registration Program)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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