새로 진단된 고위험 골육종 환자에서 선행 MAP 화학요법 종료 시 투여하는 B7-H3-CAR T 세포의 효능 평가
신규 진단된 고위험 골육종 환자에서 초기 Map 화학요법 종료 시 투여되는 B7-H3-CAR T 세포의 효능을 평가하는 2상 연구
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.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
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.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 2 단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Julie Park, MD
- 전화번호: 888-226-4343
- 이메일: referralinfo@stjude.org
연구 연락처 백업
- 이름: Judith Durrell
- 전화번호: 888-226-4343
- 이메일: referralinfo@stjude.org
연구 장소
-
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Tennessee
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Memphis, Tennessee, 미국, 38105-2794
- 모병
- St. Jude Children's Research Hospital
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수석 연구원:
- Julie Park, MD
-
연락하다:
- Julie Park, MD
- 전화번호: 888-226-4343
- 이메일: referralinfo@stjude.org
-
-
참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
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Participant and/or legally authorized representative has signed the Informed Consent Form for this study
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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.
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No evidence of progressive disease since enrolled on study
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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
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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
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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)
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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.
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Participant and/or legally authorized representative has signed the Informed Consent Form for the treatment phase of this study.
Exclusion Criteria:
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Major surgical adverse event related to the primary tumor local control defined as Clavien-Dindo category 3 requiring ongoing wound care.
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Evidence of clinically significant encephalopathy/new focal neurologic deficits.
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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
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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
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Pregnant or breastfeeding
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Presence of any condition that, in the opinion of the investigator, would prohibit the participant from undergoing treatment under this protocol
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
|
실험적: 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 |
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Event-free survival (EFS), defined as time from SJCARB7H3-41BBL infusion to disease relapse, progressive disease, new systemic therapy, secondary malignancy or death
기간: 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
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Overall survival (OS), defined as time from SJCARB7H3-41BBL cell infusion to all-cause mortality.
기간: 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
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Number of participants experiencing protocol-specified regimen-related toxicities.
기간: Time from SJCARB7H3-41BBL infusion up to 28 days post-infusion.
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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.
|
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Number of participants with successful manufacture of SJCARB7H3-41BBL cells of sufficient dose and planned product administration
기간: 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
|
공동 작업자 및 조사자
수사관
수사관
- 수석 연구원: Julie Park, MD, St. Jude Children's Research Hospital
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- 3CAR4OS
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
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 공유 기간
Data will be made available at the time of article publication.
IPD 공유 액세스 기준
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 공유 지원 정보 유형
- 연구_프로토콜
- 수액
- ICF
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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