CD30 양성 림프종에 대한 구성적 IL7R(C7R) 변형 은행 동종 CD30.CAR EBVSTS (CABAL2)
재발성 또는 불응성 CD30 양성 림프종 환자의 구성적 IL7R(C7R) 변형 은행 동종 CD30 키메라 항원 수용체 엡스타인-바 바이러스 특이적 T 림프구(CD30.CAR-EBVST)
This study involves patients with diffuse large B cell lymphoma (DLBCL), natural killer/T-cell lymphoma (NKTL), or classical Hodgkin lymphoma (cHL) (referred to collectively as lymphoma) whose disease has returned or not responded to treatment.
Previous research combined antibodies and T cells to treat cancer. Antibodies bind to foreign substances, and T cells are infection-fighting white blood cells that can kill tumor cells. Both approaches have shown promise but have not been sufficient to cure most patients. In prior studies, an antibody targeting CD30, a protein found on some T cells and cancer cells, was joined to T cells through gene transfer to create CD30.CAR T cells.
Another study showed encouraging responses using CD30.CAR T cells made from a patient's own blood and returned to the same patient (autologous cells). In an ongoing study, patients have been treated with CD30.CAR T cells derived from healthy donors (allogeneic cells), allowing use of banked cells without individualized manufacturing. This approach has shown promising clinical activity with no safety concerns to date.
In this study, investigators are evaluating CD30.CAR-EBVST cells modified with an additional molecule called C7R, which has been shown in laboratory studies to enhance anti-cancer effects. The study aims to assess the safety and effectiveness of these allogeneic, banked C7R-modified CD30.CAR-EBVST cells and determine whether they may help treat lymphoma.
As an added safety measure, the modified T cells include a marker called iC9. If significant side effects occur, patients may receive rimiducid, which can eliminate the infused T cells. Rimiducid is not yet FDA approved but has been tested in patients without significant side effects.
연구 개요
상태
정황
개입 / 치료
상세 설명
This is a Phase 1 dose-escalation study evaluating allogeneic C7R.CD30.CAR-EBVST cells in patients with relapsed or refractory CD30-positive lymphoma.
Participants are treated in sequential cohorts at one of four dose levels of C7R.CD30.CAR-EBVST cells. Treatment begins at the lowest dose level, and subsequent cohorts are treated at higher dose levels if the preceding dose is determined to be safe. If significant toxicity is observed, dose escalation may be halted, reduced, or discontinued. The relationship between dose level and both safety and potential clinical benefit is evaluated.
Prior to treatment, participants undergo screening evaluations including laboratory testing, imaging studies, and confirmation of CD30 expression. Human leukocyte antigen (HLA) testing is performed to identify the most appropriate partially matched cell line from a bank of allogeneic C7R.CD30.CAR-EBVST products.
Participants may receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine prior to infusion, as clinically appropriate, to reduce endogenous lymphocytes and support expansion of the infused cells.
C7R.CD30.CAR-EBVST cells are administered as a single intravenous infusion at the assigned dose level. Premedication may be given to reduce the risk of infusion-related reactions. Participants are monitored in the clinical setting following infusion and are required to remain within close proximity to the treatment center for a defined period to allow for monitoring of potential adverse events.
Following treatment, participants undergo scheduled follow-up evaluations including physical examinations, laboratory testing, and imaging studies to assess safety and disease status. Blood samples are collected at multiple time points after infusion to evaluate persistence of the infused cells. Tumor assessments are performed using imaging and, when clinically indicated, biopsy.
Participants demonstrating an objective clinical response following initial dosing may be considered for up to three (3) additional infusions of C7R.CD30.CAR-EBVST cells, at the discretion of the treating clinical team.
Participants are followed longitudinally after treatment, with more frequent assessments early after infusion and less frequent long-term follow-up, for up to 15 years after the most recent infusion.
연구 유형
등록 (추정된)
단계
- 1단계
연락처 및 위치
연구 연락처
- 이름: Premal Lulla, MD
- 전화번호: 713-441-1450
- 이메일: pdlulla@houstonmethodist.org
연구 연락처 백업
- 이름: Vicky Torrano, RN
- 전화번호: (832) 824-7821
- 이메일: vxtorran@texaschildrens.org
연구 장소
-
-
Texas
-
Houston, Texas, 미국, 77030
- 모병
- Houston Methodist Hospital
-
연락하다:
- Vicky Torrano, RN
- 전화번호: 832-824-7821
- 이메일: vxtorran@texaschildrens.org
-
연락하다:
- Premal Lulla, MD
- 전화번호: 713-441-1450
- 이메일: pdlulla@houstonmethodist.org
-
Houston, Texas, 미국, 77030
- 아직 모집하지 않음
- Texas Children's Hospital
-
연락하다:
- Vicky Torrano, RN
- 전화번호: 832-824-7821
- 이메일: vxtorran@texaschildrens.org
-
연락하다:
- Helen Heslop, MD
- 이메일: hheslop@bcm.edu
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
-
Diagnosis and clinical course falling into one of the following categories:
- Hodgkin lymphoma
- CD30+ aggressive B-cell lymphoma
- ALK-negative anaplastic T cell lymphoma or other peripheral T- cell lymphoma
- ALK-positive anaplastic T cell lymphoma
-
CD30-positive tumor as assayed in a CLIA certified Pathology Laboratory.
-
Age 12 to 75.
-
Bilirubin less than or equal to 2 times the upper limit of normal (except for Gilbert syndrome, where the criteria will be Bilirubin less than or equal to 3 times the upper limit of normal).
-
AST less than 3 times the upper limit of normal.
-
Estimated GFR > 70 mL/min.
-
Pulse oximetry of > 90% on room air
-
Karnofsky or Lansky score of > 60%.
-
Recovered from all acute non-hematologic toxic effects of all prior chemotherapy.
-
Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
-
Informed consent explained to, understood by and signed by patient or guardian. Patient or guardian given a copy of the informed consent form.
Exclusion Criteria:
- Received an investigational cell therapy or vaccine within the past 6 weeks.
- Received an investigational small molecule drug within the past 2 weeks.
- Received anti-CD30 antibody-based therapy within the previous 4 weeks.
- History of hypersensitivity reactions to murine protein-containing products.
- Pregnant or lactating.
- Tumor in a location where enlargement could cause airway obstruction (determined at the investigators' discretion).
- Current use of systemic corticosteroids at a dose equivalent to or higher than 10 mg/day of prednisone.
- Active significant, uncontrolled bacterial, viral or fungal infection.
- Symptomatic cardiac disease (NYHA Class III or IV disease).
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Treatment Phase
Four dose levels will be evaluated based on safety data from our current study of CD30 CAR T cells. Cohorts of three patients will be enrolled at each dose level The dose is based on the number of CD.30 CAR-EBVT-expressing cells administered. The total number of dose levels evaluated will depend upon toxicities experienced. Dose level cohorts will be numbered sequentially.
|
The dose is based on the number of CD30.CAR- expressing cells. In our previous study the highest dose was 4 × 10^8 cells/m2 and we did not reach an MTD. On Day 0, patients will receive their planned dose of investigational T cell product by IV infusion over approximately 1 to 10 minutes in an expected volume of 1 to 50 mL.
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Dose Limiting Toxicity (DLT)
기간: 28 days
|
Dose-limiting toxicity (DLT) is defined as any of the following considered possibly, probably, or definitely related to study cellular products: (1) Grade 5 event without disease progression; (2) CRS: Grade 4, or Grade 3 not improving to ≤Grade 2 within 72 hours despite therapy; (3) ICANS: Grade 4, or Grade 3 not improving within 72 hours despite therapy; (4) Grade ≥3 IEC-HS; (5) Grade ≥3 acute GvHD requiring corticosteroids and not resolving within 7 days, or steroid-refractory Grade 2 GvHD; (6) Grade 4 neutropenia or thrombocytopenia not resolving to ≤Grade 2 within 42 days, or Grade 3 thrombocytopenia with major bleeding; (7) Grade ≥3 vital organ toxicity (except transient hepatic/renal abnormalities resolving within 7 days); (8) other Grade 3 toxicities not resolving within 72 hours; (9) Grade ≥2 allergic reaction. |
28 days
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Rate of Anti-Tumor effect Objective Response (OR)
기간: 6 to 8 weeks post CTL infusion
|
Objective response rate is defined as complete response and partial response |
6 to 8 weeks post CTL infusion
|
|
Duration of response
기간: Up to 5 years
|
Response duration will be measured from the time of initial response until documented tumor progression. |
Up to 5 years
|
|
Stable disease (SD) rate
기간: 6 to 8 weeks post CTL infusion
|
SD will be defined as the proportion of patients that have stable disease |
6 to 8 weeks post CTL infusion
|
|
Duration of SD
기간: Up to 5 years
|
Stable disease is measured from the start of the treatment until the criteria for progression are met. |
Up to 5 years
|
|
Progression free survival (PFS)
기간: Up to 5 years
|
PFS is defined as the time from treatment until objective tumor progression or death, whichever occurs first. |
Up to 5 years
|
공동 작업자 및 조사자
협력자
수사관
- 수석 연구원: Helen Heslop, MD, Baylor College of Medicine
- 수석 연구원: Premal Lulla, MD, The Methodist Hospital Research Institute
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- H-56523, CABAL2
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .