A Phase 1/2 Study of a Fully Human BCMA-targeting CAR (CT103A) in Patients With Relapsed/Refractory Multiple Myeloma (FUMANBA-1) (FUMANBA-1)
2021年11月21日 更新者:Nanjing IASO Biotherapeutics Co.,Ltd
Phase 1/2 Clinical Study on Fully Human BCMA Chimeric Antigen Receptor Autologous T Cell Injection (CT103A) in the Treatment of Patients With Relapsed/Refractory Multiple Myeloma
This study is a single-armed, open-label, multicenter Phase 1/2 study to evaluate the efficacy and safety of CT103A in subjects with relapsed and refractory MM.
調査の概要
詳細な説明
Leukapheresis procedure will be performed to manufacture CT103A chimeric antigen receptor (CAR) modified T cells.
Bridging therapy is allowed between PBMC collection and lymphodepletion.
Lymphodepletion with fludarabine and cyclophosphamide was performed for three consecutive days.
After 1-day rest, subjects will receive a single dose infusion of CT103A at 1.0 x 10^6 CAR+ T cells/Kg.
Subjects will be followed in the study for a minimum of 2 years after CT103A infusion.
Long-term follow-up for lentiviral vector safety will be followed for up to 15 years after CT103A infusion.
研究の種類
介入
入学 (予想される)
132
段階
- フェーズ2
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前:Songbai Cai
- 電話番号:+86 025-58287610
- メール:simon@iasobio.com
研究場所
-
-
-
Beijing、中国
- 募集
- Peking University First Hospital
-
Beijing、中国
- 募集
- Beijing Boren Hospital
-
コンタクト:
- Kai Hu
-
Chongqing、中国
- 募集
- Xinqiao Hospital, Army Medical University
-
Shanghai、中国
- 募集
- Fudan University Zhongshan Hospital
-
Shanghai、中国
- 募集
- Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
-
Tianjin、中国
- 募集
- Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
-
-
Anhui
-
Hefei、Anhui、中国
- 募集
- Anhui Provincial Cancer Hospital
-
-
Henan
-
Zhengzhou、Henan、中国
- 募集
- The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital
-
コンタクト:
- Yongping Song
-
-
Hubei
-
Wuhan、Hubei、中国
- 募集
- Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
-
コンタクト:
- ChunRui Li
-
-
Hunan
-
Changsha、Hunan、中国
- 募集
- The Third Xiangya Hospital Of Central South University
-
-
Jiangsu
-
Nanjing、Jiangsu、中国
- 募集
- Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University
-
Nanjing、Jiangsu、中国
- 募集
- The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital
-
Xuzhou、Jiangsu、中国
- 募集
- The Affiliated Hospital of Xuzhou Medical University
-
-
Zhejiang
-
Hangzhou、Zhejiang、中国
- 募集
- The first Affiliated Hospital, Zhejiang University School of Medicine
-
コンタクト:
- He Huang
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年~70年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
Subjects must satisfy all the following criteria to be enrolled in the study:
- age 18 to 70 years old, male or female.
- Subjects with diagnosed relapsed or refractory MM according to IMWG criteria and have had at least 3 prior lines of therapy including chemotherapy based on proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). Disease progression must be documented during or within 12 months following the most recent anti-myeloma treatment.
- Evidence of cell membrane BCMA expression, as determined by a validated immunohistochemistry (IHC) or flow cytometry of tumor tissue (e.g., bone marrow biopsies, or plasmacytoma).
The subjects should have measurable disease based on at least one of the following parameters:
- The proportion of primitive immature or monoclonal plasma cells detected by bone marrow cytology, bone marrow biopsy, or flow cytometry is ≥ 5%.
- Serum M-protein ≥ 0.5 g/dL.
- Urine M-protein ≥ 200 mg/24 hrs.
- For those whose Serum or Urine M-protein does not meet the measurable criteria but the light chain type, serum free light chain (sFLC): involved sFLC level ≥ 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal.
- ECOG performance score 0-1.
- Estimated life expectancy ≥ 12 weeks.
Patients should have adequate organ function:
- Hematology: Absolute neutrophil count (ANC) ≥1×10^9 /L (prior use of growth factor support is permitted, but subjects must not have received supportive treatment within 7 days prior to laboratory examination); absolute lymphocyte count (ALC) ≥0.3×10^9 /L; platelets ≥50×10^9 /L (subjects must not have received blood transfusion support within 7 days prior to laboratory examination); hemoglobin ≥60 g/L (subjects must not have received transfusion of red blood cells [RBC] within 7 days prior to laboratory examination; the use of recombinant human erythropoietin is permitted).
- Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); total serum bilirubin ≤ 1.5×ULN.
- Renal function: Creatinine clearance rate (CrCl) calculated according to Cockcroft-Gault formula ≥ 40 ml/min.
- Coagulation function: Fibrinogen ≥ 1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, prothrombin time (PT) ≤ 1.5×ULN.
- SpO2 > 91%.
- Left ventricular ejection fraction (LVEF) ≥ 50%.
- The subject and his/her spouse agree to use an effective contraceptive tool or medication (excluding safety period contraception) for one year from the date of the subject's informed consent to the date of CAR T cell infusion.
- Subject must sign the informed consent form approved by ethics board in person before starting any screening procedure.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
- Subjects who are known to have GVHD or need long-term immunosuppressive therapy.
- Subjects have received an autologous hematopoietic stem cell transplantation (auto-HSCT) within 12 weeks before leukapheresis or have a previous history of two times of allo-HSCT or previous history of an allogeneic hematopoietic stem cell transplantation (allo-HSCT).
- Insufficient mononuclear cells for CAR T cell production.
- Subjects have received any anti-cancer treatment as follows: targeted therapies, epigenetic therapy or invasive experimental instruments therapy within 14 days or at least 5 half-lives before leukapheresis (according to the longer time), or monoclonal antibody for treating multiple myeloma within 21 days before leukapheresis, or cytotoxic therapy or proteasome inhibitors within 14 days before leukapheresis, or immunomodulatory agents within 7 days before leukapheresis.
- Subjects who were receiving a used therapeutic dose of corticosteroid treatment (defined as prednisone or equivalent > 20mg) within 7 days prior to screening, except for physiological alternatives, inhalation, or topical use.
- Subjects with serious heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmias.
- Subjects with systemic diseases that the investigator determined to be unstable include, but are not limited to, severe liver and kidney or metabolic diseases requiring medical treatment.
- Subjects with second malignancies in addition to MM within the past 5 years before the screening, exceptions to this criterion: successfully treated cervical carcinoma in situ and non-metastatic basal or squamous cell skin carcinoma, local prostate cancer after radical surgery, and ductal carcinoma in situ of the breast after radical surgery.
- Subjects with a history of organ transplantation.
- Subjects have central nervous system (CNS) involvement (including cranial neuropathies or mass lesions and leptomeningeal disease).
- Subjects with extramedullary lesions (except for a single extramedullary lesion with a maximum transverse diameter of 3 cm).
- Subjects with plasma cell leukemia.
- Subjects have received major surgery within 2 weeks prior to leukapheresis or plan to receive surgery during the study or within 2 weeks after the study treatment (excluding local anesthesia).
- Subjects participated in another interventional clinical study 3 months before signing the informed consent (ICF);
- Subjects with any uncontrolled active infection needed to receive systemic therapy within 7 days before leukapheresis collection (excluding < CTCAE grade 2 urogenital infection and upper respiratory infection).
Positive for any of the following tests:
- Hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis B core antibody-positive and detectable HBV DNA in peripheral blood
- Hepatitis C virus (HCV) antibody and hepatitis C virus RNA in peripheral blood
- Human immunodeficiency virus (HIV) antibody
- Cytomegalovirus (CMV) DNA
- Treponema Pallidum antibody
- Pregnant or lactating women.
- Subjects with mental illness or consciousness disorder or disease of the central nervous system
- Subjects who haven't recovery to Grade 1 or baseline of any toxicities due to prior treatments, excluding alopecia.
- Other conditions that researchers consider inappropriate for inclusion.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
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:CT103A in relapsed and refractory multiple myeloma patients
CT103A autologous CAR-T cells will be infused at RP2D of 1.0 x 10^6 CAR+ T cells after receiving lymphodepleting chemotherapy
|
CT103A は、完全ヒト単鎖可変フラグメント (scFv) を持つ独自の CAR 構造を含む抗 BCMA CAR レンチウイルス ベクターで形質導入された自己 T リンパ球で構成されています。
|
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 |
---|---|---|
Phase 1: Incidence and Severity of Adverse Events
時間枠:Minimum of 2 years post CT103A infusion
|
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
|
Minimum of 2 years post CT103A infusion
|
Phase 1: Laboratoty tests
時間枠:Minimum of 2 years post CT103A infusion
|
Abnormal results of laboratoty tests
|
Minimum of 2 years post CT103A infusion
|
Phase 1: Vital signs
時間枠:Minimum of 2 years post CT103A infusion
|
Abnormal results of vital signs
|
Minimum of 2 years post CT103A infusion
|
Phase 1: Physical examination
時間枠:Minimum of 2 years post CT103A infusion
|
Abnormal results of physical examination
|
Minimum of 2 years post CT103A infusion
|
Phase 2: Overall response rate (ORR) evaluated by an Independent Review Committee (IRC)
時間枠:3 months post CT103A infusion
|
Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by an IRC
|
3 months post CT103A infusion
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Overall response rate (ORR) evaluated by the investigators
時間枠:3 months post CT103A infusion
|
Percentage of subjects who achieved partial response (PR) or better according to IMWG Uniform Response Criteria for Multiple Myeloma as assessed by the investigators
|
3 months post CT103A infusion
|
Overall Survival (OS)
時間枠:Minimum of 2 years post CT103A infusion
|
Time from CT103A infusion to time of death due to any cause
|
Minimum of 2 years post CT103A infusion
|
Duration of Response (DOR)
時間枠:Minimum of 2 years post CT103A infusion
|
Time from first response evaluated by an IRC or investigators to disease progression or death from any cause
|
Minimum of 2 years post CT103A infusion
|
Progression-free Survival (PFS)
時間枠:Minimum of 2 years post CT103A infusion
|
Time from CT103A infusion to first documentation of progressive disease (PD), or death due to any cause, whichever occurs first
|
Minimum of 2 years post CT103A infusion
|
Time to Response (TTR)
時間枠:Minimum of 2 years post CT103A infusion
|
Time from CT103A infusion to first documentation of response evaluated by an IRC or investigators
|
Minimum of 2 years post CT103A infusion
|
Laboratoty tests
時間枠:Minimum of 2 years post CT103A infusion
|
Abnormal results of laboratoty tests
|
Minimum of 2 years post CT103A infusion
|
Vital signs
時間枠:Minimum of 2 years post CT103A infusion
|
Abnormal results of vital signs
|
Minimum of 2 years post CT103A infusion
|
Physical examination
時間枠:Minimum of 2 years post CT103A infusion
|
Abnormal results of physical examination
|
Minimum of 2 years post CT103A infusion
|
Minimal Residual Disease (MRD)
時間枠:Minimum of 2 years post CT103A infusion
|
Proportion of subjects who achieved MRD negative
|
Minimum of 2 years post CT103A infusion
|
Pharmacokinetics - Cmax
時間枠:Minimum of 2 years post CT103A infusion
|
The maximum transgene level at Tmax
|
Minimum of 2 years post CT103A infusion
|
Pharmacokinetics - Tmax
時間枠:Minimum of 2 years post CT103A infusion
|
Time to peak transgene level
|
Minimum of 2 years post CT103A infusion
|
Pharmacokinetics - AUC0-28days
時間枠:Minimum of 2 years post CT103A infusion
|
Area under the curve of CAR T cells from time zero to Day 28
|
Minimum of 2 years post CT103A infusion
|
Pharmacokinetics - AUC0-90days
時間枠:Minimum of 2 years post CT103A infusion
|
Area under the curve of CAR T cells from time zero to Day 90
|
Minimum of 2 years post CT103A infusion
|
soluble BCMA levels
時間枠:Minimum of 2 years post CT103A infusion
|
soluble BCMA levels in peripheral blood of subjects
|
Minimum of 2 years post CT103A infusion
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Immunogenicity
時間枠:Minimum of 2 years post CT103A infusion
|
Development of an anti-CAR antibody response
|
Minimum of 2 years post CT103A infusion
|
replication competent lentivirus (RCL)
時間枠:Minimum of 2 years post CT103A infusion
|
The incidence of replication competent lentivirus (RCL)
|
Minimum of 2 years post CT103A infusion
|
the levels of CAR-T related inflammatory factors
時間枠:Minimum of 2 years post CT103A infusion
|
the levels of CRP, IL-6 and Ferritin
|
Minimum of 2 years post CT103A infusion
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者:Lugui Qiu, MD, PhD、Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
- 主任研究者:Chunrui Li, MD, PhD、Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2020年4月1日
一次修了 (予想される)
2022年10月1日
研究の完了 (予想される)
2024年6月1日
試験登録日
最初に提出
2021年9月22日
QC基準を満たした最初の提出物
2021年9月23日
最初の投稿 (実際)
2021年10月4日
学習記録の更新
投稿された最後の更新 (実際)
2021年11月23日
QC基準を満たした最後の更新が送信されました
2021年11月21日
最終確認日
2021年9月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
CT103Aの臨床試験
-
Chunrui LiNanjing IASO Biotherapeutics Co.,Ltd募集
-
Peking University People's Hospitalまだ募集していません
-
Nanjing IASO Biotherapeutics Co.,Ltdまだ募集していません
-
Nanjing IASO Biotherapeutics Co.,Ltdまだ募集していません
-
Tongji HospitalNanjing IASO Biotechnology Co., Ltd.募集多発性硬化症 | 神経系の自己免疫疾患 | 自己免疫疾患 | 重症筋無力症 | 視神経脊髄炎スペクトラム障害 | 自己免疫性脳炎 | 特発性炎症性ミオパシー | 慢性炎症性脱髄性多発神経根神経障害 | ミエリンオリゴデンドロサイト糖タンパク質抗体関連疾患 (MOGAD) | POEMS症候群中国