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A Phase 1/2 Study of a Fully Human BCMA-targeting CAR (CT103A) in Patients With Relapsed/Refractory Multiple Myeloma (FUMANBA-1) (FUMANBA-1)

21 novembre 2021 mis à jour par: 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.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Anticipé)

132

Phase

  • Phase 2
  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

  • Nom: Songbai Cai
  • Numéro de téléphone: +86 025-58287610
  • E-mail: simon@iasobio.com

Lieux d'étude

  • Chine
      • Beijing, Chine
        • Recrutement
        • Peking University First Hospital
      • Beijing, Chine
        • Recrutement
        • Beijing Boren Hospital
        • Contact:
          • Kai Hu
      • Chongqing, Chine
        • Recrutement
        • Xinqiao Hospital, Army Medical University
      • Shanghai, Chine
        • Recrutement
        • Fudan University Zhongshan Hospital
      • Shanghai, Chine
        • Recrutement
        • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
      • Tianjin, Chine
        • Recrutement
        • Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    • Anhui
      • Hefei, Anhui, Chine
        • Recrutement
        • Anhui Provincial Cancer Hospital
    • Henan
      • Zhengzhou, Henan, Chine
        • Recrutement
        • The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital
        • Contact:
          • Yongping Song
    • Hubei
      • Wuhan, Hubei, Chine
        • Recrutement
        • Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
        • Contact:
          • ChunRui Li
    • Hunan
      • Changsha, Hunan, Chine
        • Recrutement
        • The Third Xiangya Hospital of Central South University
    • Jiangsu
      • Nanjing, Jiangsu, Chine
        • Recrutement
        • Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University
      • Nanjing, Jiangsu, Chine
        • Recrutement
        • The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital
      • Xuzhou, Jiangsu, Chine
        • Recrutement
        • The Affiliated Hospital of Xuzhou Medical University
    • Zhejiang
      • Hangzhou, Zhejiang, Chine
        • Recrutement
        • The first Affiliated Hospital, Zhejiang University School of Medicine
        • Contact:
          • He Huang

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 70 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

Subjects must satisfy all the following criteria to be enrolled in the study:

  1. age 18 to 70 years old, male or female.
  2. 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.
  3. 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).

  4. 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.
  5. ECOG performance score 0-1.
  6. Estimated life expectancy ≥ 12 weeks.

  7. 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%.
  8. 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.
  9. 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:

  1. Subjects who are known to have GVHD or need long-term immunosuppressive therapy.
  2. 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).
  3. Insufficient mononuclear cells for CAR T cell production.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. Subjects with a history of organ transplantation.
  10. Subjects have central nervous system (CNS) involvement (including cranial neuropathies or mass lesions and leptomeningeal disease).
  11. Subjects with extramedullary lesions (except for a single extramedullary lesion with a maximum transverse diameter of 3 cm).
  12. Subjects with plasma cell leukemia.
  13. 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).
  14. Subjects participated in another interventional clinical study 3 months before signing the informed consent (ICF);
  15. 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).

  16. 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
  17. Pregnant or lactating women.
  18. Subjects with mental illness or consciousness disorder or disease of the central nervous system
  19. Subjects who haven't recovery to Grade 1 or baseline of any toxicities due to prior treatments, excluding alopecia.
  20. Other conditions that researchers consider inappropriate for inclusion.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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
Médicament: CT103A
CT103A se compose de lymphocytes T autologues transduits avec un vecteur lentiviral anti-BCMA CAR contenant une structure CAR unique avec un fragment variable à chaîne unique (scFv) entièrement humain.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Phase 1: Incidence and Severity of Adverse Events
Délai: 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
Délai: Minimum of 2 years post CT103A infusion
Abnormal results of laboratoty tests
Minimum of 2 years post CT103A infusion
Phase 1: Vital signs
Délai: Minimum of 2 years post CT103A infusion
Abnormal results of vital signs
Minimum of 2 years post CT103A infusion
Phase 1: Physical examination
Délai: 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)
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Overall response rate (ORR) evaluated by the investigators
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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
Délai: Minimum of 2 years post CT103A infusion
Abnormal results of laboratoty tests
Minimum of 2 years post CT103A infusion
Vital signs
Délai: Minimum of 2 years post CT103A infusion
Abnormal results of vital signs
Minimum of 2 years post CT103A infusion
Physical examination
Délai: Minimum of 2 years post CT103A infusion
Abnormal results of physical examination
Minimum of 2 years post CT103A infusion
Minimal Residual Disease (MRD)
Délai: Minimum of 2 years post CT103A infusion
Proportion of subjects who achieved MRD negative
Minimum of 2 years post CT103A infusion
Pharmacokinetics - Cmax
Délai: Minimum of 2 years post CT103A infusion
The maximum transgene level at Tmax
Minimum of 2 years post CT103A infusion
Pharmacokinetics - Tmax
Délai: Minimum of 2 years post CT103A infusion
Time to peak transgene level
Minimum of 2 years post CT103A infusion
Pharmacokinetics - AUC0-28days
Délai: 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
Délai: 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
Délai: Minimum of 2 years post CT103A infusion
soluble BCMA levels in peripheral blood of subjects
Minimum of 2 years post CT103A infusion

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
Immunogenicity
Délai: 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)
Délai: 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
Délai: Minimum of 2 years post CT103A infusion
the levels of CRP, IL-6 and Ferritin
Minimum of 2 years post CT103A infusion

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Nanjing IASO Biotherapeutics Co.,Ltd

Les enquêteurs

  • Chercheur principal: Lugui Qiu, MD, PhD, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
  • Chercheur principal: Chunrui Li, MD, PhD, Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 avril 2020

Achèvement primaire (Anticipé)

1 octobre 2022

Achèvement de l'étude (Anticipé)

1 juin 2024

Dates d'inscription aux études

Première soumission

22 septembre 2021

Première soumission répondant aux critères de contrôle qualité

23 septembre 2021

Première publication (Réel)

4 octobre 2021

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

23 novembre 2021

Dernière mise à jour soumise répondant aux critères de contrôle qualité

21 novembre 2021

Dernière vérification

1 septembre 2021

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • XL-LCYJ-0007

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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