Immunoglobulin Replacement Therapy (IgRT) Versus Antibiotic Prophylaxis (PA) in Patients Treated by CD19-targeted Chimeric Antigen Receptor (CAR)T Cells for a B Cell Acute Lymphoblastic Leukemia or a B Cell Lymphoma (PREV-CART)
A Multicentric Phase III Randomized Clinical Trial Open-label, Comparing Immunoglobulin Replacement Therapy (IgRT) and Antibiotic Prophylaxis (AP) in Patients Treated by CD19-targeted Chimeric Antigen Receptor (CAR)T Cells for a B Cell Acute Lymphoblastic Leukemia or a B Cell Lymphoma
B cell (CD19) targeted chimeric antigen receptor modified T Cells (CAR-T) has transformed treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) or B-cell lymphoma (BCL).
Because patients receiving CAR-T often present uncontrolled disease and have undergone several lines of treatment, they may be deeply immuno-depressed and prone to infections. Hypogammaglobulinemia were reported in 74% of patients preCAR-T cells infusion (Hill JA, et al. Blood Rev. 2019 Nov). CART cells also results in depletion of normal CD19+ B cells and hypogammaglobulinemia as an on-target, off tumor toxicity.
Because CAR-T cells can persist for years, patients are exposed to infectious complications secondary to long-term Bcell aplasia and severe hypogammaglobulinemia (<4g/l). Data from patients who received rituximab (CD20-specific monoclonal antibody) show that patients with severe hypogammaglobulinemia experienced recurrent bronchitis, sinusitis, pneumonia, and rarely, enteroviral meningoencephalitis. In patients receiving CAR T-cells, infection density is 0.55-0.67 infections/100 days3,5 at risk after the first month with a majority of respiratory and ENT (earsnose-throat) infections. To prevent infections, anti-bacterial prophylaxis (AP) based on local guidelines is often used in patients treated by CAR-T cells, with the risk of subsequent resistance. Otherwise, intravenous immunoglobulin replacement therapy (IgRT) is authorized by the French authorities for patients with secondary antibody deficiencies who developed severe or recurrent infections after appropriate antimicrobial therapy, if IgG levels <4g/l. However, although IgRT as primary prophylaxis (PP) have no approval, they are used as PP after CAR T-cells by many centers, with no data supporting such a strategy. The benefit of IgRT over AP as a primary prophylaxis in the setting of CD19 CAR-T cells therapy should be demonstrated given its burden for patients and care, as well as its cost and the risk of Ig shortage. Therefore, this multi-centric prospective randomized openlabel study aims to assess the benefits of IgRT versus AP as PP in patients with secondary antibody deficiencies.
연구 개요
상태
연구 유형
등록 (추정된)
단계
- 3단계
연락처 및 위치
연구 연락처
- 이름: Jérôme Lambert, MD PhD
- 전화번호: +33 +33 1 42 49 97 42
- 이메일: jerome.lambert@u-paris.fr
연구 연락처 백업
- 이름: Florence Rabian, MD
- 전화번호: +33 +33 1 42 38 51 27
- 이메일: florence.rabian@aphp.fr
참여기준
자격 기준
공부할 수 있는 나이
- 어린이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
Inclusion Criteria:
- Age 16-80 years at inclusion
- B-cell acute lymphoblastic leukemia or a B-cell lymphoma
- With gamma globulins <4g/L at the time of screening
- Receiving CD19-targeted autologous CAR-T cells (with AMM in their indication)
- Patients with childbearing potential* should have reliable contraception for the all duration of the study and another 12 months after CAR-T infusion.
- Contraceptive measures for concerned patients
- Informed consent signed by patient or legal representatives
Exclusion Criteria:
- Any medical history of intolerance to intravenous immunoglobulin
- With renal failure calculated glomerular filtrate rate <30 mL / min;
- With hepatic failure or hepatitis or bilirubin> 3 times the upper limit of normal, Serum ALT/AST >=5N
- With existing serious acute infection
- Contraindication to immunoglobulin or to prophylactic antibiotherapy administered in this clinical trial
- No health insurance coverage
- Females who are pregnant or breastfeeding
- Participation in another interventional study or being
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 방지
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Immunoglobulin Replacement therapy
|
IgRT 0.4g/Kg IV every 4 weeks for 12 months
|
|
활성 비교기: Antibiotic prophylaxis
|
PA following each center's guidelines, for 12 months
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Occurrence of recurrent infections
기간: At 12 months
|
Defined by at least 2 episodes requiring a curative systemic antibiotic treatment
|
At 12 months
|
|
Occurrence of a severe infection
기간: At 12 months
|
Defined by the need of hospitalization
|
At 12 months
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Cumulative hazard of severe infections
기간: Up to 12 months
|
requiring hospitalization
|
Up to 12 months
|
|
Infection-free survival rate
기간: Up to 12 months
|
Up to 12 months
|
|
|
Occurrence of COVID19 infection
기간: Up to 12 months
|
Up to 12 months
|
|
|
Cumulative incidence of readmissions due to infectious episode after hospital discharge following the infusion of CART cells
기간: Up to 12 months
|
Up to 12 months
|
|
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Incidence of adverse events due to IgRT and/or PA
기간: Up to 12 months
|
Up to 12 months
|
|
|
Dosage of immune markers
기간: Up to 12 months
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts, at lymphodepletion
|
Up to 12 months
|
|
Dosage of immune markers
기간: At 1 month
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts
|
At 1 month
|
|
Dosage of immune markers
기간: At 3 months
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts
|
At 3 months
|
|
Dosage of immune markers
기간: At 6 months
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts
|
At 6 months
|
|
Dosage of immune markers
기간: At 9 months
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts
|
At 9 months
|
|
Dosage of immune markers
기간: At 12 months
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts
|
At 12 months
|
|
Quality of life assessment
기간: At 3 months
|
EQ5D5L : standardized measure of health-related quality of life assessing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
The EQ-5D-5L index score typically ranges from values below 0 (health states considered worse than death) to 1.0 (full health), depending on the country-specific value set.
Higher scores indicate better health-related quality of life.
|
At 3 months
|
|
Quality of life assessment
기간: At 6 months
|
EQ5D5L : standardized measure of health-related quality of life assessing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
The EQ-5D-5L index score typically ranges from values below 0 (health states considered worse than death) to 1.0 (full health), depending on the country-specific value set.
Higher scores indicate better health-related quality of life.
|
At 6 months
|
|
Quality of life assessment
기간: At 9 months
|
EQ5D5L : standardized measure of health-related quality of life assessing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
The EQ-5D-5L index score typically ranges from values below 0 (health states considered worse than death) to 1.0 (full health), depending on the country-specific value set.
Higher scores indicate better health-related quality of life.
|
At 9 months
|
|
Quality of life assessment
기간: At 12 months
|
EQ5D5L : standardized measure of health-related quality of life assessing five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
The EQ-5D-5L index score typically ranges from values below 0 (health states considered worse than death) to 1.0 (full health), depending on the country-specific value set.
Higher scores indicate better health-related quality of life.
|
At 12 months
|
|
Quality of life assessment
기간: At 3 months
|
EORTC QLQ-C30 : cancer-specific questionnaire designed to assess health-related quality of life in patients with cancer.
Scores are linearly transformed to a 0-100 scale.
For the Global Health Status/Quality of Life scale and the functional scales, higher scores indicate better quality of life and functioning.
For symptom scales, higher scores indicate greater symptom burden and poorer health status.
|
At 3 months
|
|
Quality of life assessment
기간: At 6 months
|
EORTC QLQ-C30 : cancer-specific questionnaire designed to assess health-related quality of life in patients with cancer.
Scores are linearly transformed to a 0-100 scale.
For the Global Health Status/Quality of Life scale and the functional scales, higher scores indicate better quality of life and functioning.
For symptom scales, higher scores indicate greater symptom burden and poorer health status.
|
At 6 months
|
|
Quality of life assessment
기간: At 9 months
|
EORTC QLQ-C30 : cancer-specific questionnaire designed to assess health-related quality of life in patients with cancer.
Scores are linearly transformed to a 0-100 scale.
For the Global Health Status/Quality of Life scale and the functional scales, higher scores indicate better quality of life and functioning.
For symptom scales, higher scores indicate greater symptom burden and poorer health status.
|
At 9 months
|
|
Quality of life assessment
기간: At 12 months
|
EORTC QLQ-C30 : cancer-specific questionnaire designed to assess health-related quality of life in patients with cancer.
Scores are linearly transformed to a 0-100 scale.
For the Global Health Status/Quality of Life scale and the functional scales, higher scores indicate better quality of life and functioning.
For symptom scales, higher scores indicate greater symptom burden and poorer health status.
|
At 12 months
|
|
Incremental Cost-Effectiveness Ratio (ICER)
기간: Up to 12 months
|
Up to 12 months
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
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
- APHP241013
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