Clinical Trials /

Study to Evaluate the Safety and Efficacy of Anti-CD38 CAR-T in Relapsed or Refractory Multiple Myeloma Patients

NCT03464916

Description:

The study is an open-label Phase 1 single dose-escalation safety study of CAR2 Anti-CD38 A2 CAR-T Cells in patients with Relapsed or Refractory Multiple Myeloma, who meet all other eligibility criteria.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Safety and Efficacy of Anti-CD38 CAR-T in Relapsed or Refractory Multiple Myeloma Patients
  • Official Title: A Phase 1, Open-Label, Dose-Escalation, Pharmacokinetic, and Pharmacodynamic Study of the Safety and Efficacy of CAR2 Anti-CD38 A2 CAR-T Cells in Patients With Relapsed or Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: SOR-CART-MM-001
  • NCT ID: NCT03464916

Conditions

  • Relapsed or Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
CAR2 Anti-CD38 A2 CAR-T CellsCAR2 Anti-CD38 A2 CAR-T Cells

Purpose

The study is an open-label Phase 1 single dose-escalation safety study of CAR2 Anti-CD38 A2 CAR-T Cells in patients with Relapsed or Refractory Multiple Myeloma, who meet all other eligibility criteria.

Detailed Description

      All subjects who received investigational CAR-T therapy will be included in the analyses and
      summaries of safety, efficacy, pharmacokinetic, and pharmacodynamic assessments.
    

Trial Arms

NameTypeDescriptionInterventions
CAR2 Anti-CD38 A2 CAR-T CellsExperimentalRelapsed or Refractory Multiple Myeloma
  • CAR2 Anti-CD38 A2 CAR-T Cells

Eligibility Criteria

        Inclusion Criteria:

          -  The patient must either have relapsed refractory multiple myeloma (RRMM) after
             receiving prior lines of anti-myeloma treatments that included at least lenalidomide
             (Revlimid®), pomalidomide (Pomalyst®), bortezomib (Velcade®), carfilzomib (Kyprolis®),
             and daratumumab (Darzalex®) (refractory MM is defined as the development of disease
             progression during therapy with an anti-myeloma regimen or within 60 days of the last
             dose of an anti-myeloma regimen or the achievement of less than a partial response
             (PR) after greater than or equal to 2 cycles; for relapsing patients the duration from
             the last dose of the last prior treatment regimen to relapse must be less than or
             equal to 12 months); OR have multiple myeloma that is refractory to or has relapsed
             within 1 year of receiving high-dose therapy [HDT]/autologous stem cell
             transplantation [ASCT] in first- or second-line (refractory is defined as the
             achievement of less than a PR at the Day 90 to 100 post-ASCT response assessment)

          -  Must have measurable disease as defined by the following: Serum M-protein greater than
             or equal to 1 g/dL; OR Urine M-protein greater than or equal to 200 mg/24 hours; OR
             Serum free light chain (FLC) assay; involved FLC level greater than or equal to 10
             mg/dL provided the serum FLC ratio is abnormal; OR greater than or equal to 30% clonal
             plasma cells in the bone marrow aspirate or biopsy sample

          -  Must have a life expectancy of at least 12 weeks

          -  Subjects should be willing and able to comply with the study schedule and protocols

          -  Females of childbearing potential must have 2 negative pregnancy tests, agree to
             ongoing pregnancy testing during the study, and sexually active female and male
             subjects must be willing to use an effective method to avoid pregnancies.

        Exclusion Criteria:

          -  Subjects who received anticancer therapy or investigational drug within 28 days of
             first dose

          -  Subjects who received any approved anticancer chemotherapy within 21 days of first
             dose (exception cyclophosphamide as NMA conditioning)

          -  Subjects with unresolved toxicity greater than Grade 2 from previous therapies

          -  Have myeloma involvement of central nervous system (CNS) or a history of brain
             metastasis or spinal cord compression

          -  Subjects with an ECOG performance status greater than or equal to 3

          -  Has received allogenic hematopoietic stem cell transplantation (HSCT) within 6 months,
             have active graft-versus-host disease (GVHD) following transplant, or receiving
             immunosuppressive therapy following a transplant

          -  Has received any CAR cell line therapies

          -  Has any clinically significant low baseline lab results for hemoglobin, platelet
             counts, and neutrophil counts, at screening unless resulting from underlying RRMM.

          -  Has any clinically significant elevated baseline lab results for serum creatinine,
             AST, and total bilirubin (except for patients in whom hyperbilirubinemia is attributed
             to Gilbert's syndrome) at screening regardless of causality.

          -  Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of
             chronic hepatitis B or C.

          -  Female subjects who are pregnant or breastfeeding

          -  Active bacterial, viral or fungal infections

          -  Has active plasma cell leukemia

          -  Has medical condition, abnormality, or psychiatric illness that would prevent study
             participation

          -  Left ventricular ejection fraction (LVEF) less than 40%
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the MTD
Time Frame:28 days
Safety Issue:
Description:The MTD is assessed according to a 3+3 dose-escalation design by the occurrence of treatment-emergent dose-limiting toxicities during the 28-day Treatment Period in the dose-escalation phase of the study

Secondary Outcome Measures

Measure:Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the Cmax
Time Frame:28 days
Safety Issue:
Description:CAR2 Anti-CD38 A2 CAR-T cell blood concentrations will be measured at different time points during the 28-day treatment period to evaluate the maximum concentration (Cmax).
Measure:Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the AUC
Time Frame:28 days
Safety Issue:
Description:CAR2 Anti-CD38 A2 CAR-T cell blood concentrations will be measured at different time points during the 28-day treatment period to evaluate the area under the curve (AUC).
Measure:Evaluate the safety of Anti-CD38 A2 CAR-T cells in Patients with RRMM by incidence of treatment-emergent adverse events
Time Frame:6 months
Safety Issue:
Description:The evaluation of safety will be measured by an assessment of the incidence of treatment-emergent adverse events for each patient in the dose-escalation and expansion phases of the study.
Measure:Assess preliminary efficacy by response rate in accordance with the modified International Myeloma Working Group (IMWG) criteria
Time Frame:6 months
Safety Issue:
Description:As a measure of activity, overall response rate will be assessed according to the modified International Myeloma Working Group (IMWG) criteria. Response will be assessed for each patient over a 6-month timeframe during both the dose-escalation and expansion phases of the protocol.
Measure:Assess preliminary efficacy by depth of response in accordance with the modified International Myeloma Working Group (IMWG) criteria.
Time Frame:6 months
Safety Issue:
Description:As a measure of activity, depth of response (ie, category of response) will be assessed according to the modified International Myeloma Working Group (IMWG) criteria. This will be assessed for each patient over a 6-month timeframe during both the dose-escalation and expansion phases of the protocol.
Measure:Assess preliminary efficacy by duration of response in accordance with the modified International Myeloma Working Group (IMWG) criteria.
Time Frame:6 months
Safety Issue:
Description:As a measure of activity, duration of response will be assessed according to the modified International Myeloma Working Group (IMWG) criteria. This will be assessed for each patient over a 6-month timeframe during both the dose-escalation and expansion phases of the protocol.
Measure:Assess preliminary efficacy by progression-free survival.
Time Frame:6 months
Safety Issue:
Description:As a measure of activity, Progression-free survival (PFS) will be assessed. The events for the assessment of PFS are disease progression and death events. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Measure:Assess preliminary efficacy by overall survival.
Time Frame:6 months
Safety Issue:
Description:As a measure of activity, Overall Survival (OS) will be assessed. The events for the assessment of OS are death events. Time to event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.
Measure:The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of treatment-emergent events.
Time Frame:6 months
Safety Issue:
Description:The RP2D will be assessed by the incidence of treatment-emergent adverse events during the Treatment and Observation Periods.
Measure:The determination of the recommended phase 2 dose will be based on an evaluation of overall response rate.
Time Frame:6 months
Safety Issue:
Description:The rate of response as a determination factor for the RP2D will be assessed by the incidence of responses of at least partial response according to the IMWG criteria during the Treatment and Observation Periods.
Measure:The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of depth of response.
Time Frame:6 months
Safety Issue:
Description:The depth of response as a determination factor for the RP2D will be assessed by the IMWG categories for response according to changes from baseline in M-protein levels in serum and urine, per cent plasma cells in the bone marrow, and size (area) of soft tissue extramedullary plasmacytomas (if applicable). This will be assessed for each patient over a 6-month timeframe during both the dose-escalation and expansion phases of the protocol.
Measure:The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of duration of response.
Time Frame:6 months
Safety Issue:
Description:The duration of response as a determination factor for the RP2D will be assessed by the IMWG criteria for disease progression following the achievement of a response of at least a partial response according to changes in M-protein levels in serum and urine, per cent plasma cells in the bone marrow, the appearance of new lytic bone lesions, and/or the development of new soft tissue extramedullary plasmacytomas during the Treatment and Observation periods.
Measure:The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of progression-free survival.
Time Frame:6 months
Safety Issue:
Description:Progression-free survival as a determination factor for the RP2D will be assessed by the IMWG criteria for disease progression events and death events. This time to event endpoint will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate. Progression-free survival will be evaluated during the Treatment and Observation Periods of the study.
Measure:The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of overall survival.
Time Frame:6 months
Safety Issue:
Description:Overall survival as a determination factor for the RP2D will be assessed by death events that occur during the Treatment and Observation Periods. Time- to-event endpoints will be estimated using Kaplan-Meier methods. Point estimates and 95% confidence intervals will be provided where appropriate.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sorrento Therapeutics, Inc.

Trial Keywords

  • CAR2 Anti-CD38 A2 CAR-T Cells

Last Updated

October 26, 2019