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

NCT ID: NCT05066646

Last Updated: 2021-11-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

132 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-01

Study Completion Date

2024-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

CT103A

Intervention Type DRUG

CT103A consists of autologous T lymphocytes transduced with anti-BCMA CAR lentiviral vector that containing a unique CAR structure with a fully human single-chain variable fragment (scFv).

Interventions

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CT103A

CT103A consists of autologous T lymphocytes transduced with anti-BCMA CAR lentiviral vector that containing a unique CAR structure with a fully human single-chain variable fragment (scFv).

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nanjing IASO Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lugui Qiu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Chunrui Li, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Tongji Hospital

Locations

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Anhui Provincial Cancer Hospital

Hefei, Anhui, China

Site Status RECRUITING

The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status RECRUITING

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

Wuhan, Hubei, China

Site Status RECRUITING

The Third Xiangya Hospital of Central South University

Changsha, Hunan, China

Site Status RECRUITING

Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Site Status RECRUITING

The Affiliated Hospital of Nanjing University Medical School, Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

Site Status RECRUITING

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

Site Status RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status RECRUITING

Beijing Boren Hospital

Beijing, , China

Site Status RECRUITING

Peking University First Hospital

Beijing, , China

Site Status RECRUITING

Xinqiao Hospital, Army Medical University

Chongqing, , China

Site Status RECRUITING

Fudan University Zhongshan Hospital

Shanghai, , China

Site Status RECRUITING

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, , China

Site Status RECRUITING

Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Tianjin, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Songbai Cai

Role: CONTACT

Phone: +86 025-58287610

Email: [email protected]

Facility Contacts

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Kaiyang Ding

Role: primary

Yongping Song

Role: primary

Chunrui Li

Role: primary

Jing Liu

Role: primary

Jianyong Li

Role: primary

Bing Chen

Role: primary

Zhenyu Li

Role: primary

He Huang

Role: primary

Kai Hu

Role: primary

Hanyun Ren

Role: primary

Xi Zhang

Role: primary

Peng Liu

Role: primary

Jianqing Mi

Role: primary

Lugui Qiu

Role: primary

References

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Keam SJ. Equecabtagene Autoleucel: First Approval. Mol Diagn Ther. 2023 Nov;27(6):781-787. doi: 10.1007/s40291-023-00673-y. Epub 2023 Sep 2.

Reference Type DERIVED
PMID: 37658205 (View on PubMed)

Zhou L, Fu W, Wu S, Xu K, Qiu L, Xu Y, Yan X, Zhang Q, Zhang M, Wang L, Hong R, Chang AH, Yu J, Fu S, Kong D, Li L, Wang Y, Li Z, Jiang H, Huang J, Liu Z, Su N, Wei G, Hu Y, Huang H. Derivation and validation of a novel score for early prediction of severe CRS after CAR-T therapy in haematological malignancy patients: A multi-centre study. Br J Haematol. 2023 Aug;202(3):517-524. doi: 10.1111/bjh.18873. Epub 2023 May 16.

Reference Type DERIVED
PMID: 37192741 (View on PubMed)

Other Identifiers

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XL-LCYJ-0007

Identifier Type: -

Identifier Source: org_study_id