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出境医 / 临床实验 / Human BCMA Targeted T Cells Injection Therapy for BCMA-positive Relapsed/Refractory Multiple Myeloma

Human BCMA Targeted T Cells Injection Therapy for BCMA-positive Relapsed/Refractory Multiple Myeloma

Study Description
Brief Summary:
To evaluate the safety and efficacy of Human BCMA Targeted T Cells Injection for the treatment of BCMA-positive relapsed/refractory multiple myeloma. Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of BCMA CAR+ T cells.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Human BCMA targeted T Cells Injection Phase 1

Detailed Description:
Participants with BCMA-positive relapsed/refractory multiple myeloma can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, Electrocardiograph, CT/MRI/PET, and blood draws. Participants receive chemotherapy prior to the infusion of BCMA CAR+ T cells. After the infusion, participants will be followed for side effects and effect of BCMA CAR+ T cells. Study procedures may be performed while hospitalized.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial to Evaluate the Safety and Efficacy of Human BCMA Targeted T Cells Injection for Subjects With BCMA-positive Relapsed/Refractory Multiple Myeloma
Actual Study Start Date : July 1, 2019
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2024
Arms and Interventions
Arm Intervention/treatment
Experimental: Human BCMA targeted T Cells Injection
A single infusion of anti-BCMA CAR transduced T cells administered intravenously at a target dose of 3 to 9 x 10^6 CAR T +cells/kg. The classic "3+3" dose escalation will be applied.
 Drug: Human BCMA targeted T Cells Injection
Autologous genetically modified anti-BCMA CAR transduced T cells
Outcome Measures
Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by NCI-CTCAE 5.0 [ Time Frame: 28 days post infusion ]

Secondary Outcome Measures :
  1. Concentration of Anti-BCMA CAR T Cells in blood [ Time Frame: 2 years post infusion ]
  2. Concentration of Anti-BCMA CAR T Cells in bone marrow [ Time Frame: 2 years post infusion ]
  3. Pharmacodynamics (Levels of Cytokines in Serum) [ Time Frame: 2 years post infusion ]
  4. Pharmacodynamics (Content of clonal plasma cells in bone marrow) [ Time Frame: 2 years post infusion ]
  5. Overall response rate (ORR) after administration [ Time Frame: 3 months post infusion ]
  6. Negative proportion of minimal residual disease (MRD) [ Time Frame: 28 days post infusion ]
  7. Duration of remission (DOR) after administration [ Time Frame: 2 years post infusion ]
  8. Progress Free Survival (PFS) after administration [ Time Frame: 2 years post infusion ]
  9. Overall Survival (OS)after administration [ Time Frame: 2 years post infusion ]
  10. Positive incidence of anti-drug antibody [ Time Frame: 2 years post infusion ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects volunteer to participate in clinical research, understand and know the research and sign informed consent document, willing to complete all the trial procedures;
  2. 18 to 70 Years Old, Male and female;
  3. Expected survival > 12 weeks;
  4. Previously diagnosed as multiple myeloma by IMWG updated criteria (2014);
  5. Patients with positive pathological test results or flow cytometry proving that BCMA expression of malignant plasma cells in bone marrow or plasma cell tumors ≥30%;

  6. One of the following indicators is satisfied:

    1. Serum M protein IgG ≥ 10 g/L, or IgA > 10 mg/L, or IgD > 5 mg/L;
    2. Urine M protein ≥ 200 mg/24h;
    3. Serum free light chain ≥ 100 mg/L;

  7. Patients with relapsed/refractory multiple myeloma. Relapsed is defined as:

    Patients have disease progression after at least three-line treatment regimens. Patients previously received at least 3 different mechanisms treatment regimens for multiple myeloma, including protease inhibitors and immunomodulators, and have disease progression within 60 days of the latest treatment ; Refractory is defined as: Patients who achieved remission in the piror therapies, have disease progression within 60 days, or after the latest therapy.

  8. Those who relapse 90 days after stem cell transplantation
  9. ECOG score 0-1;

  10. Liver, kidney and cardiopulmonary functions meet the following requirements:

    1. Creatinine clearance (estimated by Cockcroft Gault formula) ≥ 40 mL/min;
    2. Left ventricular ejection fraction >50%;
    3. Baseline peripheral oxygen saturation >95%;
    4. Total bilirubin ≤ 2×ULN; ALT and AST ≤2.5 × ULN;
  11. The venous access required for collection can be established, and no leukocyte collection contraindications.

Exclusion Criteria:

  1. Accompanied by other uncontrolled malignancies;
  2. Subjects with positive HBsAg or HBcAb and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; syphilis primary screening antibody positive;
  3. Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), severe arrhythmia, liver, kidney or metabolic disease with poor drug control;
  4. Patients who are accounted to be not appropriate for this trail by investigator;
  5. Pregnant or lactating, or planning to have a pregnancy during or within 1 year after treatment;
  6. Received CAR-T treatment or other gene therapies before enrollment;
  7. Those who failed to sign informed consent form or comply with the research procedures; Unwilling or unable to comply with research requirements;
  8. Have had severe immediate hypersensitivity reactions to any drugs used in this research;
  9. The presence or suspicion of fungi, bacteria, viruses or other infections that are uncontrollable or requiring intravenous treatment;
  10. In the past two years, the terminal organ was damaged due to autoimmune diseases (such as crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the systemic use of immunosuppressive or other systemic disease control drugs was required;
  11. Have a history of central nervous system (CNS) disease, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain damage, dementia, Parkinson's disease, psychosis.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Hongliang Fang, doctor 021-58552006 fanghongliang@dashengbio.com

Locations
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China, Henan
The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine Recruiting
Zhengzhou, Henan, China
Contact: Zhi Cheng, M.D.    +(86)-139-3852-6995    clinicaltrials.chengzhi@outlook.com   
China, Shanghai
Shanghai Changzheng Hospital Recruiting
Shanghai, Shanghai, China, 200003
Contact: Weijun Fu, Professor    021-81885423    fuweijun2010@hotmail.com   
China, Zhejiang
The First Affiliated Hospital of Wenzhou Medical University Recruiting
Wenzhou, Zhejiang, China, 325000
Contact: Kang Yu, Professor    0577-55579486    yukang62@126.com   
Sponsors and Collaborators
Hrain Biotechnology Co., Ltd.
Shanghai Changzheng Hospital
First Affiliated Hospital of Wenzhou Medical University
The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine
Tracking Information
First Submitted Date  ICMJE June 24, 2019
First Posted Date  ICMJE July 1, 2019
Last Update Posted Date March 1, 2021
Actual Study Start Date  ICMJE July 1, 2019
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 28, 2019) 		Number of participants with treatment-related adverse events as assessed by NCI-CTCAE 5.0 [ Time Frame: 28 days post infusion ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 28, 2019)
  • Concentration of Anti-BCMA CAR T Cells in blood [ Time Frame: 2 years post infusion ]
  • Concentration of Anti-BCMA CAR T Cells in bone marrow [ Time Frame: 2 years post infusion ]
  • Pharmacodynamics (Levels of Cytokines in Serum) [ Time Frame: 2 years post infusion ]
  • Pharmacodynamics (Content of clonal plasma cells in bone marrow) [ Time Frame: 2 years post infusion ]
  • Overall response rate (ORR) after administration [ Time Frame: 3 months post infusion ]
  • Negative proportion of minimal residual disease (MRD) [ Time Frame: 28 days post infusion ]
  • Duration of remission (DOR) after administration [ Time Frame: 2 years post infusion ]
  • Progress Free Survival (PFS) after administration [ Time Frame: 2 years post infusion ]
  • Overall Survival (OS)after administration [ Time Frame: 2 years post infusion ]
  • Positive incidence of anti-drug antibody [ Time Frame: 2 years post infusion ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Human BCMA Targeted T Cells Injection Therapy for BCMA-positive Relapsed/Refractory Multiple Myeloma
Official Title  ICMJE A Phase I Clinical Trial to Evaluate the Safety and Efficacy of Human BCMA Targeted T Cells Injection for Subjects With BCMA-positive Relapsed/Refractory Multiple Myeloma
Brief Summary To evaluate the safety and efficacy of Human BCMA Targeted T Cells Injection for the treatment of BCMA-positive relapsed/refractory multiple myeloma. Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of BCMA CAR+ T cells.
Detailed Description Participants with BCMA-positive relapsed/refractory multiple myeloma can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, Electrocardiograph, CT/MRI/PET, and blood draws. Participants receive chemotherapy prior to the infusion of BCMA CAR+ T cells. After the infusion, participants will be followed for side effects and effect of BCMA CAR+ T cells. Study procedures may be performed while hospitalized.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE Drug: Human BCMA targeted T Cells Injection
Autologous genetically modified anti-BCMA CAR transduced T cells
Study Arms  ICMJE Experimental: Human BCMA targeted T Cells Injection
A single infusion of anti-BCMA CAR transduced T cells administered intravenously at a target dose of 3 to 9 x 10^6 CAR T +cells/kg. The classic "3+3" dose escalation will be applied.
Intervention: Drug: Human BCMA targeted T Cells Injection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 28, 2019) 		18
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2024
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subjects volunteer to participate in clinical research, understand and know the research and sign informed consent document, willing to complete all the trial procedures;
  2. 18 to 70 Years Old, Male and female;
  3. Expected survival > 12 weeks;
  4. Previously diagnosed as multiple myeloma by IMWG updated criteria (2014);
  5. Patients with positive pathological test results or flow cytometry proving that BCMA expression of malignant plasma cells in bone marrow or plasma cell tumors ≥30%;

  6. One of the following indicators is satisfied:

    1. Serum M protein IgG ≥ 10 g/L, or IgA > 10 mg/L, or IgD > 5 mg/L;
    2. Urine M protein ≥ 200 mg/24h;
    3. Serum free light chain ≥ 100 mg/L;

  7. Patients with relapsed/refractory multiple myeloma. Relapsed is defined as:

    Patients have disease progression after at least three-line treatment regimens. Patients previously received at least 3 different mechanisms treatment regimens for multiple myeloma, including protease inhibitors and immunomodulators, and have disease progression within 60 days of the latest treatment ; Refractory is defined as: Patients who achieved remission in the piror therapies, have disease progression within 60 days, or after the latest therapy.

  8. Those who relapse 90 days after stem cell transplantation
  9. ECOG score 0-1;

  10. Liver, kidney and cardiopulmonary functions meet the following requirements:

    1. Creatinine clearance (estimated by Cockcroft Gault formula) ≥ 40 mL/min;
    2. Left ventricular ejection fraction >50%;
    3. Baseline peripheral oxygen saturation >95%;
    4. Total bilirubin ≤ 2×ULN; ALT and AST ≤2.5 × ULN;
  11. The venous access required for collection can be established, and no leukocyte collection contraindications.

Exclusion Criteria:

  1. Accompanied by other uncontrolled malignancies;
  2. Subjects with positive HBsAg or HBcAb and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; syphilis primary screening antibody positive;
  3. Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), severe arrhythmia, liver, kidney or metabolic disease with poor drug control;
  4. Patients who are accounted to be not appropriate for this trail by investigator;
  5. Pregnant or lactating, or planning to have a pregnancy during or within 1 year after treatment;
  6. Received CAR-T treatment or other gene therapies before enrollment;
  7. Those who failed to sign informed consent form or comply with the research procedures; Unwilling or unable to comply with research requirements;
  8. Have had severe immediate hypersensitivity reactions to any drugs used in this research;
  9. The presence or suspicion of fungi, bacteria, viruses or other infections that are uncontrollable or requiring intravenous treatment;
  10. In the past two years, the terminal organ was damaged due to autoimmune diseases (such as crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the systemic use of immunosuppressive or other systemic disease control drugs was required;
  11. Have a history of central nervous system (CNS) disease, such as epilepsy, seizures, paralysis, aphasia, stroke, severe brain damage, dementia, Parkinson's disease, psychosis.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Hongliang Fang, doctor 021-58552006 fanghongliang@dashengbio.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04003168
Other Study ID Numbers  ICMJE HRAIN01-MM01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hrain Biotechnology Co., Ltd.
Study Sponsor  ICMJE Hrain Biotechnology Co., Ltd.
Collaborators  ICMJE
  • Shanghai Changzheng Hospital
  • First Affiliated Hospital of Wenzhou Medical University
  • The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine
Investigators  ICMJE Not Provided
PRS Account Hrain Biotechnology Co., Ltd.
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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