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Clinical Trial to Evaluate BCMA Car-T (CT053) in Patients With Relapsed and/or Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT03975907
Recruitment Status : Not yet recruiting
First Posted : June 5, 2019
Last Update Posted : June 5, 2019
Sponsor:
Collaborators:
Beijing Chao Yang Hospital
The First Affiliated Hospital of Soochow University
Information provided by (Responsible Party):
Carsgen Therapeutics, Ltd.

Brief Summary:
This is an open-label, single arm study to evaluate the safety and tolerability of treatment with CT053 CAR-BCMA T in patients with relapsed and/or refractory multiple myeloma.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: CAR-BCMA T Cells Phase 1 Phase 2

Detailed Description:
The study is composed of two stages, Phase I stage is for dose escalation and recommendation of phase 2 dose, and Phase II stage is to Detailed Description: verify the efficacy and safety of the dose proposed.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Phase I is an open-label, dose escalation study and 4 cohorts to evaluate the safety and tolerability of treatment with CT053 and to determine maximum tolerable dose (MTD) and the Recommended Phase 2 Dose (RP2D) for CT053.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Phase I/II Clinical Trial to Evaluate the Safety and Efficacy of Fully Human Anti-BCMA Chimeric Antibody Receptor Autologous T Cell (CAR T) Infusion in Patients With Relapsed and/or Refractory Multiple Myeloma
Estimated Study Start Date : June 1, 2019
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : December 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: CAR-BCMA T Cells
The subjects are enrolled into 4 dose levels cohorts in sequence
Biological: CAR-BCMA T Cells
The CAR-BCMA T cells (study drug) used in this study are chimeric antigen receptor specifically expressing T cells targeting BCMA.




Primary Outcome Measures :
  1. Phase 1, Safety and tolerability: dose limiting toxicity [ Time Frame: 28days post administration of CAR-T-cells ]
    dose limiting toxicity

  2. Phase 2, efficacy of CT053 CAR-BCMA T cells: overall response rate [ Time Frame: 12 months post administration of CAR-T-cells ]
    overall response rate (ORR)=(sCR+CR+VGPR+PR)


Secondary Outcome Measures :
  1. Efficacy evaluation after 12 weeks of CT053 CAR-BCMA T cells infusion: Overall Response Rate [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Overall Response Rate(ORR), ORR=(sCR+CR+VGPR+PR)/total subjects.

  2. Efficacy evaluation after 12 weeks of CT053 CAR-BCMA T cells infusion: Response rate [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Response rate of VGPR, CR and sCR.

  3. Pharmacokinetics (the cell persistence duration in peripheral blood) [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Duration of CAR-BCMA T-Cell persistence is the period from the day of infusion to the first negative test result or result lower than the detection limit.

  4. Pharmacokinetics (the number of cell copies in peripheral blood) [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Pharmacokinetics is the "Implantation endpoint" which is defined as the number of copies of CAR-BCMA DNA in peripheral blood detected by q-PCR and flow cytometer at each visit after infusion until any two consecutive test results are negative or below the detection limit.

  5. Safety and tolerability after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: Occurrence rate and severity of AE [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Occurrence rate and severity of AE after infusion.

  6. Safety and tolerability after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: Occurrence rate and severity [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Occurrence rate and severity of treatment related AE.

  7. Safety and tolerability after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: Occurrence rate and severity [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Occurrence rate and severity of AEs of special interest (CRS, CRES, etc.)

  8. Safety and tolerability after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: Positive rate [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Positive rate of Anti-CT053 CAR-BCMA T cell.

  9. Efficacy evaluation after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: Overall Response Rate [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Overall Response Rate(ORR), ORR=(sCR+CR+VGPR+PR)/total subjects.

  10. Efficacy evaluation after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: Duration of Response [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Duration of Response (DOR )

  11. Efficacy evaluation after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: Clinical Benefit Rate [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Clinical Benefit Rate (CBR), CBR=ORR+MR

  12. Efficacy evaluation after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: Time to Response [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Time to Response (TTR)

  13. Efficacy evaluation after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: MRD negative rate [ Time Frame: through 24 months post administration of CAR-T-cells ]
    MRD negative rate

  14. Efficacy evaluation after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: Progression Free Survival [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Progression Free Survival (PFS)

  15. Efficacy evaluation after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: Overall Survival [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Overall Survival (OS)

  16. Efficacy evaluation after 12 months and 24 months of CT053 CAR-BCMA T cells infusion: Response rate [ Time Frame: through 24 months post administration of CAR-T-cells ]
    Response rate of VGPR, CR and sCR.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients and legally acceptable representative must have voluntarily signed ICF and willing to complete the study procedure, after fully understanding of the study.
  2. Age ≥ 18 years, male or female
  3. The patients have received at least 3 prior regimen for MM, (Induction therapy followed by autologous transplantation[ASCT] and maintenance therapy represents one line of therapy, those who have not been treated with ASCT should have documented rationale); For each line of therapy, the patient should have received at least one standard treatment cycle (2016 IMWG) unless the best response to the treatment line is documented as progressive diseases (PD)
  4. The patients should have received treatment with at least one proteasome inhibitor AND one immunomodulatory drug, AND, should have ever fail, intolerant or relapse/refractory to either or both of the treatments.;
  5. The patient should be relapsed to the last therapy within 12 months, or refractory to the last therapy within 60 days (meet the definition of progressive disease in 2016 IMWG) and must have documented medical records
  6. The patients should have measurable disease based on at least one of the following parameters:

    • Serum M-protein ≥ 10 g/L;
    • Urine M-protein ≥ 200 mg/24 hrs;
    • For those whose Serum or Urine M- protein dose not meed the measurable criteria but the light chain type, serum free light chain (FLC): involved FLC level ≥ 10 mg/dL (100 mg/L) provided serum FLC ratio is abnormal
  7. Estimated life expectancy > 12 weeks
  8. ECOG performance score 0-1;
  9. Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis
  10. Patients should maintain adequate organ function
  11. Women of childbearing age must undergo a serum pregnancy test with negative results before screening and lymphodepletion preconditioning with fludarabine and cyclophosphamide, and are willing to use effective and reliable method of contraception for at least 1 year after T cell infusion
  12. Men who actively have intercourse with child-bearing potential women must be willing to use effective and reliable method of contraception for at least 1 year after T cell infusion

Exclusion Criteria:

  1. Pregnant or lactating women;
  2. Patients with human immunodeficiency virus (HIV), syphilis, hepatitis C virus (HCV) positive; Hepatitis B surface antigen (HbsAg) positive and Deoxyribonucleic acid of hepatitis B virus (HBV-DNA)≥200 IU/mLor ≥103 copies/mL
  3. Patients with any uncontrolled active infection including but not limited to active tuberculosis.
  4. Patients with AEs from previous treatment that have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) ≤ 1, excluding hair loss, neuropathy and other events that the treating physician can determine to be tolerable.
  5. Patients who have ever had any CAR T cell therapy;
  6. Patients who have ever had anti-BCMA therapy;
  7. Patients have received allogeneic stem cell transplantation for treating multiple myeloma;
  8. Patients have received autologous stem cell transplantation less than 12 weeks before leukapheresis;
  9. Patients have received any anti-cancer treatment within 14 days before leukapheresis including but not limited to cytotoxic therapy, proteasome inhibitors, immunomodulatory agents, targeted therapies, epigenetic therapy or experimental drug therapy. If the field of radiation covers ≤ 5% of the bone marrow, the subjects are eligible to participate in the study regardless of the radiotherapy end date;
  10. Patients have received ≥ 5 mg prednisone daily or other equivalent dose of steroids within 14 days before leukapheresis or lymphodepletion;
  11. Patients have plasma cell leukemia, Waldenström macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome or AL amyloidosis;
  12. Patients have been administered live attenuated vaccine 4 weeks before leukapheresis or lymphodepletion
  13. Patients allergic to component of study treatment.
  14. Patients have any of the condition as following within 6 months of ICF sign-off: New York Heart Association (NYHA) stage III or IV congestive heart failure, angina pectoris, myocardial infarction, coronary artery bypass graft, stroke (excluding lacunar stroke), history of clinically significant arrhythmia including but not limited to ventricular arrhythmia, significant QT interval prolongation, uncontrolled blood pressure as defined as systolic > 160 mmHg, diastolic > 100 mmHg, uncontrolled diabetes mellitus, pulmonary thrombolism, other conditions that investigators believe that participating in this clinical trial may endanger the health of the patients
  15. Patients are known to have active autoimmune diseases including but not limited to psoriasis, rheumatoid arthritis and other needs of long-term immunosuppressive therapy
  16. patients are oxygen dependent as defined by the blood oxygen saturation (finger oxygen detection method) can be maintained > 95% only by oxygen inhalation before leukapheresis
  17. Patients with second malignancies in addition to MM are not eligible if the second malignancy has required treatment within the past 5 years or is not in complete remission. There are two exceptions to this criterion: successfully treated cervical carcinoma in situ and non-metastatic basal cell skin carcinoma
  18. Patients have central nervous system (CNS) metastases or CNS involvement (including cranial neuropathies or mass lesions and leptomeningeal disease). Patients with history of spinal cord compression from MM are eligible provided spinal cord compression has been treated with surgery or radiation at least 28 days prior to study entry
  19. Patients are unable or unwilling to comply with the requirements of clinical trial
  20. Patients have received major surgery 2 weeks prior to leukapheresis or 4 weeks prior to lymphodepletion and after the study treatment (excluding cataract and other local anesthesia)
  21. Patients are relatives to investigator or his/her staff, or those who may have an interest in the investigator and/or his/her staff.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03975907


Contacts
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Contact: Zonghai LI, MD 8621-64355922 zonghaili@carsgen.com
Contact: Xiaochen DONG 8621-64355922 xiaochendong@carsgen.com

Sponsors and Collaborators
Carsgen Therapeutics, Ltd.
Beijing Chao Yang Hospital
The First Affiliated Hospital of Soochow University
Investigators
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Principal Investigator: Wenming CHEN, MD Beijing Chao Yang Hospital
Principal Investigator: Zhengzheng FU, MD The First Affiliated Hospital of Soochow University

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Responsible Party: Carsgen Therapeutics, Ltd.
ClinicalTrials.gov Identifier: NCT03975907     History of Changes
Other Study ID Numbers: CT053-MM-01
First Posted: June 5, 2019    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Carsgen Therapeutics, Ltd.:
multiple myeloma
car-T

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases