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.
調査の概要
状態
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Jérôme Lambert, MD PhD
- 電話番号：+33 +33 1 42 49 97 42
- メール：jerome.lambert@u-paris.fr
研究連絡先のバックアップ
- 名前：Florence Rabian, MD
- 電話番号：+33 +33 1 42 38 51 27
- メール：florence.rabian@aphp.fr
参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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
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：防止
- 割り当て：ランダム化
- 介入モデル：並列代入
- 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：Immunoglobulin Replacement therapy
|
IgRT 0.4g/Kg IV every 4 weeks for 12 months
|
|
アクティブコンパレータ：Antibiotic prophylaxis
|
PA following each center's guidelines, for 12 months
|
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 |
|---|---|---|
|
Occurrence of recurrent infections
時間枠：At 12 months
|
Defined by at least 2 episodes requiring a curative systemic antibiotic treatment
|
At 12 months
|
|
Occurrence of a severe infection
時間枠：At 12 months
|
Defined by the need of hospitalization
|
At 12 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Cumulative hazard of severe infections
時間枠：Up to 12 months
|
requiring hospitalization
|
Up to 12 months
|
|
Infection-free survival rate
時間枠：Up to 12 months
|
Up to 12 months
|
|
|
Occurrence of COVID19 infection
時間枠：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
時間枠：Up to 12 months
|
Up to 12 months
|
|
|
Incidence of adverse events due to IgRT and/or PA
時間枠：Up to 12 months
|
Up to 12 months
|
|
|
Dosage of immune markers
時間枠：Up to 12 months
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts, at lymphodepletion
|
Up to 12 months
|
|
Dosage of immune markers
時間枠：At 1 month
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts
|
At 1 month
|
|
Dosage of immune markers
時間枠：At 3 months
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts
|
At 3 months
|
|
Dosage of immune markers
時間枠：At 6 months
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts
|
At 6 months
|
|
Dosage of immune markers
時間枠：At 9 months
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts
|
At 9 months
|
|
Dosage of immune markers
時間枠：At 12 months
|
IgA, IgG, IgM, CD19/CD4/CD8 lymphocytes counts
|
At 12 months
|
|
Quality of life assessment
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：Up to 12 months
|
Up to 12 months
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
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
追加の関連 MeSH 用語
その他の研究ID番号
- APHP241013
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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