Clinical Trials /

Safety and Efficacy of IM21 Car-t Cells in Patients With Recurrent or Refractory BCMA Positive Multiple Myeloma

NCT03711864

Description:

In patients with multiple myeloma with recurrent or refractory BCMA, car-t cell infusion was performed after screening, blood collection and pretreatment. Starting dose for 5 x 10 ^ 5 / kg, 1 x 10 ^ 6 doses sequentially. If dose-limiting toxicity is not observed in 3 patients in a dose group, the next dose group test can be performed; If more than 2/3 of patients (2 cases, included) in a dose group had DLT, dose-escalation was not performed. If 1 case of DLT (1/3) appears in the first 3 patients of a dose group, 3 patients need to be added to the dose group (at this time, there are 6 patients in the group).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of IM21 Car-t Cells in Patients With Recurrent or Refractory BCMA Positive Multiple Myeloma
  • Official Title: Safety and Efficacy of IM21 Car-t Cells in Patients With Recurrent or Refractory BCMA Positive Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: YMCART201804
  • NCT ID: NCT03711864

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
IM21 CARTIM 21IM21 CART

Purpose

In patients with multiple myeloma with recurrent or refractory BCMA, car-t cell infusion was performed after screening, blood collection and pretreatment. Starting dose for 5 x 10 ^ 5 / kg, 1 x 10 ^ 6 doses sequentially. If dose-limiting toxicity is not observed in 3 patients in a dose group, the next dose group test can be performed; If more than 2/3 of patients (2 cases, included) in a dose group had DLT, dose-escalation was not performed. If 1 case of DLT (1/3) appears in the first 3 patients of a dose group, 3 patients need to be added to the dose group (at this time, there are 6 patients in the group).

Detailed Description

      In patients with multiple myeloma with recurrent or refractory BCMA, car-t cell infusion was
      performed after screening, blood collection and pretreatment. Starting dose for 5 x 10 ^ 5 /
      kg, 1 x 10 ^ 6 doses sequentially. If dose-limiting toxicity is not observed in 3 patients in
      a dose group, the next dose group test can be performed; If more than 2/3 of patients (2
      cases, included) in a dose group had DLT, dose-escalation was not performed. If 1 case of DLT
      (1/3) appears in the first 3 patients of a dose group, 3 patients need to be added to the
      dose group (at this time, there are 6 patients in the group). If DLT occurs in 1 of the 3
      patients (with or without) or 2 of the 6 patients (with or without), no further dose
      escalation is allowed. Researchers and bidders to form drug safety monitoring committee
      (SRC), every dose group of subjects to complete the DLT observation period, after summarizing
      the security of this dose group, determine the test of the next dose, subjects such as draw
      up the highest dose group safety tolerance, SRC to decide whether to continue to increase the
      dose group of research, finally according to have obtained all the safety and efficacy of
      dose group information to determine the recommended dose (RP2D).Dose-limiting toxicity (DLT)
    

Trial Arms

NameTypeDescriptionInterventions
IM21 CARTExperimentalAll patients will be treated with fludarabine and cyclophosphamide for 3 days,then,CAR-T cells expressing BCMA CAR will be infused 24-96 hours later.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  1) the patient has suffered from multiple myeloma (according to the updated diagnostic
                 criteria of IMWG)Need to meet one or more of the following: • elevated blood calcium
                 (> 11.5 mg/dL) > 2.65 tendency/L, renal insufficiency (creatinine > 2 mg/dL) [177
                 (including mol/L or higher] or creatinine clearance < 40 ml/min, anemia (hemoglobin <
                 10 g/dL and hemoglobin below normal floor > 2 g/dL), bone disease (soluble osseous
                 lesions or osteoporosis) in X-ray radiography and CT bone or PET - CT found in more
                 than one place or bone lesionsOr in compliance with any of the following: • bone
                 marrow clonal plasma cells greater than or equal to 60% • abnormal serum free light
                 chain ratio greater than or equal to 100 (involvement) or <0.01 (involvement) • focal
                 lesions of >1 found by functional imaging examination including PET/CT and/or
                 whole-body MRI2) immunohistochemistry or flow cytometry detection of positive BCMA
                 expression in patients with refractory recurrent multiple myeloma;Refractory
                 definition: 1) at least through second-line treatment with bortezomib or lenadamine or
                 2) clinician determination.Definition of recurrence: see NCCN clinical guidelines for
                 multiple myeloma (2016.v2), including post-transplant recurrence.3) age: 18 to 80
                 years old;4) the expected survival period is more than 3 months;5) score 0-2 for ECOG
                 (refer to annex 2)6) hemoglobin (Hb) is greater than or equal to 80g/L; Neutrophil
                 count absolutely (ANC) > 1 x 10 ^ 9 / L; The platelet total (PLT) 50 x 10 ^ 9 or
                 higher/L.Volunteer to participate in the test and sign the informed consent
    
            Exclusion Criteria:
    
              -  1) patients with high-risk viscera involvement: tumor invading central nervous system,
                 gastrointestinal tract, lung, pericardium, one of the large vessels;2) those who have
                 graft versus host reaction and need to use immunosuppressive agents; Or people with
                 autoimmune diseases;3) patients who used chemotherapy or radiotherapy within 3 days
                 before blood sampling;4) a combination of systemic steroid use within 5 days before
                 the blood collection period (except for recent or current use of inhaled steroids);5)
                 use drugs to stimulate the production of bone marrow hematopoietic cells within 5 days
                 before the blood collection period (such as elevating white needle);6) have used any
                 gene therapy products before;7) history of epilepsy or other diseases of the central
                 nervous system;8) New York heart association (NYHA) class for Ⅲ above (see attachment
                 3);9) the normal upper limit of creatinine >1.5 times or ALT/AST>3 times or bilirubin
                 >2 times;10) active hepatitis b or c, HIV or other uncured active infected persons;11)
                 pregnant or lactating women;12) patients with other uncontrolled diseases, which are
                 deemed inappropriate by researchers;Any condition that may increase the risk of the
                 subject or interfere with the results of the study.
          
    Maximum Eligible Age:80 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Occurrence of study related adverse events
    Time Frame:2 years
    Safety Issue:
    Description:defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical events) that are possibly, likely, or definitely related to study treatment Adverse events assessed according to NCI-CTCAE v4.0 criteria 2.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Peking Union Medical College Hospital

    Last Updated