新たに診断された高リスク骨肉腫患者に対する初期MAP化学療法終了時におけるB7-H3-CAR T細胞投与の有効性評価
新たに診断された高リスク骨肉腫患者における前線MAP化学療法終了時投与のB7-H3-CAR T細胞の有効性を評価する第II相試験
The purpose of this study is to assess the safety, feasibility, and effectiveness of a consolidative B7-H3 CAR T cell therapy in patients with newly diagnosed high-risk osteosarcoma who have undergone upfront standard chemotherapy.
Primary Objectives:
- To evaluate 1-year RFS from the time of SJCARB7H3-41BBL infusion for patients with newly diagnosed metastatic osteosarcoma who received standard chemotherapy.
Secondary Objectives:
- To evaluate the OS from time of SJCARB7H3-41BBL infusion for patients with newly diagnosed metastatic osteosarcoma who received standard chemotherapy.
- To evaluate the feasibility of delivering SJCARB7H3-41BBL at the end of standard therapy in patients with newly diagnosed metastatic osteosarcoma.
- To describe the safety of autologous SJCARB7H3-41BBL therapy when delivered at the end of standard therapy in patients with newly diagnosed metastatic osteosarcoma.
調査の概要
状態
条件
詳細な説明
This is a phase 2 study of SJCARB7H3-41BBL for participants with newly diagnosed high-risk metastatic osteosarcoma who received standard chemotherapy.
All participants will receive standard chemotherapy (for example methotrexate, anthracycline, platinum), local control surgery, and pulmonary metastasectomy if applicable, and this is not considered part of protocol therapy. Participants will undergo apheresis prior to standard local control surgery (about 12 weeks after diagnosis) for SJCARB7H3-41BBL manufacture and then resume standard consolidation therapy. A safety run will initiate with Regimen A. For Regimen A, eligible participants with available SJCARB7H3-41BB product will receive lymphodepletion chemotherapy 14-28 days after the completion of standard chemotherapy (31 weeks after diagnosis), followed by SJCARB7H3-41BB infusion. If Regimen A is not cleared, then Regimen B will be evaluated, where lymphodepletion and SJCARB7H3-41BB infusion occur post pulmonary metastasectomy. Following successful clearance of either regimen A or, if necessary, regimen B, then the efficacy cohort will be initiated. Participants will be followed with serial disease evaluations for 2 years from SJCARB7H3-41BB infusion prior to transfer to our institutional long-term follow-up (LTFU) protocol. The total duration from completion of standard therapy, including experimental therapy and follow-up on 3CAR4OS, is approximately 2 years.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Julie Park, MD
- 電話番号：888-226-4343
- メール：referralinfo@stjude.org
研究連絡先のバックアップ
- 名前：Judith Durrell
- 電話番号：888-226-4343
- メール：referralinfo@stjude.org
研究場所
-
-
Tennessee
-
Memphis、Tennessee、アメリカ、38105-2794
- 募集
- St. Jude Children's Research Hospital
-
主任研究者：
- Julie Park, MD
-
コンタクト：
- Julie Park, MD
- 電話番号：888-226-4343
- メール：referralinfo@stjude.org
-
-
参加基準
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:
-
Participant and/or legally authorized representative has signed the Informed Consent Form for this study
-
Prior cancer therapy:
- Regimen A only: Completed all planned cycles of consolidation therapy between 14-28 days prior.
- Regimen B only: has completed all planned cycles of consolidation chemotherapy at least 14 days prior and if clinically indicated, participant has undergone pulmonary metastasectomy. They must have recovered from any surgical complications with no ongoing sequelae of category 2 or higher by the Clavien-Dindo classification system and less than 6 weeks must have passed from time of pulmonary metastasectomy.
-
No evidence of progressive disease since enrolled on study
-
Lansky performance status score of ≥ 50 for participants <16 years of age or Karnofsky score ≥ 50 for participants ≥ 16 years. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status
-
Adequate organ function as indicated by:
- Renal: Serum creatinine ≤ 1.5 X the upper limit of normal (ULN) based on enrollment eligibility table.
- Hepatic: Total bilirubin ≤ 3 times ULN for age OR conjugated bilirubin ≤ 2 mg/dL AND ALT (SGPT) ≤ 5 times ULN
- Cardiac: Shortening fraction ≥ 28% OR ejection fraction ≥ 50% as measured by echocardiogram
- Respiratory: Oxygen saturation ≥ 90% on room air without supplemental oxygen or mechanical ventilation
-
Laboratory values meet the following criteria:
- Absolute Neutrophil Count (ANC) ≥ 750 cells/uL
- Platelet Count of ≥ 75,000 (can be transfused)
- Hemoglobin ≥ 7 g/dL (can be transfused)
-
Participant is ≥ 7 days from receiving supra-physiologic dosing of systemic (IV or PO) corticosteroids. Glucocorticosteroid physiologic replacement therapy for management of adrenal insufficiency is allowed.
-
Participant and/or legally authorized representative has signed the Informed Consent Form for the treatment phase of this study.
Exclusion Criteria:
-
Major surgical adverse event related to the primary tumor local control defined as Clavien-Dindo category 3 requiring ongoing wound care.
-
Evidence of clinically significant encephalopathy/new focal neurologic deficits.
-
Presence of active severe infection, defined as:
- positive blood culture within 48 hours of enrollment, OR
- fever above 38.2° C, AND clinical signs of infection within 48 hours of enrollment
-
Participant has received prior disease-directed therapy other than 1st line therapy with methotrexate, an anthracycline, and a platinum and local control surgery
• Regimen B only - okay to have undergone initial pulmonary metastasectomy
-
Pregnant or breastfeeding
-
Presence of any condition that, in the opinion of the investigator, would prohibit the participant from undergoing treatment under this protocol
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）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：3CAR4OS Treatment
All patients will receive standard of care chemotherapy, which is not considered part of protocol therapy. Eligible patients will undergo apheresis prior to standard local control surgery for CAR T cell manufacture and then resume standard therapy. In the absence of progressive disease, eligible patients with available SJCARB7H3-41BBL product will receive lymphodepletion chemotherapy (fludarabine/cyclophosphamide) after the completion of standard chemotherapy, followed by SJCARB7H3-41BBL infusion. Pulmonary metastasectomy will be performed as indicated according to the standard of care and will be timed after (Regimen A) or before (Regimen B) lymphodepletion and SJCARB7H3-41BBL infusion. Following successful clearance of either regimen A or, if necessary, regimen B, the efficacy cohort will be initiated. |
IV IV IV prior to and again at 3, 6, and 9 hours following each dose of cyclophosphamide. IV collection 1X107 CAR+ T cells/kg |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Event-free survival (EFS), defined as time from SJCARB7H3-41BBL infusion to disease relapse, progressive disease, new systemic therapy, secondary malignancy or death
時間枠：Time from SJCARB7H3-41BBL infusion to time of first event, followed up to 24-months post-infusion
|
Event-free participants will be censored at the time of last follow-up. This analysis will report the Kaplan-Meier (KM) curve, along with the 12-month EFS estimate and its 80% confidence interval using the arcsine-square root transformation. Evaluable participants are those who complete standard chemotherapy, receive SJCARB7H3-41BBL and are treated on the regimen used for the Efficacy phase. |
Time from SJCARB7H3-41BBL infusion to time of first event, followed up to 24-months post-infusion
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall survival (OS), defined as time from SJCARB7H3-41BBL cell infusion to all-cause mortality.
時間枠：Time from SJCARB7H3-41BBL infusion to time of death from any cause, followed up to 24-months post-infusion
|
Event-free participants will be censored at the time of last follow-up. OS will be reported similarly to the EFS endpoint on the same participant subset. |
Time from SJCARB7H3-41BBL infusion to time of death from any cause, followed up to 24-months post-infusion
|
|
Number of participants experiencing protocol-specified regimen-related toxicities.
時間枠：Time from SJCARB7H3-41BBL infusion up to 28 days post-infusion.
|
This outcome measure will be descriptively summarized for the overall participant group and by regimen (if more than 1 regimen is evaluated) for each regimen-related toxicity. Evaluable participants include those who receive SJCARB7H3_41BBL and remain on protocol therapy through at least 28 days post-infusion or experience a related unacceptable toxicity. |
Time from SJCARB7H3-41BBL infusion up to 28 days post-infusion.
|
|
Number of participants with successful manufacture of SJCARB7H3-41BBL cells of sufficient dose and planned product administration
時間枠：Time of SJCARB7H3-41BBL infusion
|
This outcome measure will be descriptively summarized for the overall participant group and by regimen (if more than 1 regimen is evaluated) for participants who undergo apheresis and remain on protocol therapy through the end of standard therapy. |
Time of SJCARB7H3-41BBL infusion
|
協力者と研究者
捜査官
- 主任研究者：Julie Park, MD、St. Jude Children's Research Hospital
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
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
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 3CAR4OS
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
IPD 共有時間枠
Data will be made available at the time of article publication.
IPD 共有アクセス基準
Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
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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