Clinical Trials /

AGENT-797 in Patients With Relapsed/Refractory Multiple Myeloma

NCT04754100

Description:

This is a Phase I, open-label, dose-escalation, single arm study to explore the safety, tolerability, and preliminary clinical activity of agenT-797, an unmodified, allogeneic iNKT cell therapy, in subjects with relapsed/refractory MM, as well as define the RP2D.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: AGENT-797 in Patients With Relapsed/Refractory Multiple Myeloma
  • Official Title: A Phase I Open-Label Study of the Safety, Tolerability and Preliminary Clinical Activity of Allogeneic Invariant Natural Killer (iNKT) Non-transduced Cells (agenT-797) in Patients With Relapsed/Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 2019-1305
  • NCT ID: NCT04754100

Conditions

  • Relapsed/Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
agenT-797Dosage and Cohorts

Purpose

This is a Phase I, open-label, dose-escalation, single arm study to explore the safety, tolerability, and preliminary clinical activity of agenT-797, an unmodified, allogeneic iNKT cell therapy, in subjects with relapsed/refractory MM, as well as define the RP2D.

Detailed Description

      This is a Phase I, open-label, dose-escalation, single arm study to explore the safety,
      tolerability, and preliminary clinical activity of agenT-797, an unmodified, allogeneic iNKT
      cell therapy, in subjects with relapsed/refractory MM, as well as define the RP2D.

      In Part 1, the study will employ a standard 3+3 dose escalation design, for which 3 to 6
      evaluable subjects (maximally 9 if recommended by the Safety Review Committee [SRC]) will be
      enrolled at each assigned dose level, per cohort depending on the occurrence of DLTs.

      Part 2 will consist of one or more cohorts of in total up to around 6 to 12 subjects with
      relapsed/refractory MM who receive agenT-797 at a given dose after lymphodepletion and will
      employ a 3+3 dose escalation/de-escalation design depending on the occurrence of DLTs. The
      starting dose in Part 2 will be equal to the maximum tolerated dose (MTD) defined in Part 1
      in the absence of any DLTs at that dose level. If a DLT is observed at the MTD in Part 1, the
      starting dose level in Part 2 will be the dose level below MTD.

      Details of the analyses will be described in a statistical analysis plan.

      A Safety Monitoring Committee will be established to assess safety and decide on escalation
      to next Cohort.
    

Trial Arms

NameTypeDescriptionInterventions
Dosage and CohortsExperimentalPart 1: Dose escalation without lymphodepletion. Dosage Frequency and Mode of Administration: agenT-797 will be administered to subjects as a single IV infusion. Part 2: Dose escalation with lymphodepletion (optional) Dosage Frequency and Mode of Administration: Subjects will receive lymphodepletion before infusion of agenT-797. Starting dose will be defined based on data from Part 1.
  • agenT-797

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent obtained prior to any screening procedures and in accordance
             with federal, local, and institutional guidelines.

          -  Age ≥ 18 years.

          -  Confirmed diagnosis, and evidence of progressive disease or clinical relapse as
             defined by International Myeloma Working Group (IMWG) criteria and following prior
             therapy for MM:

               1. Relapsed or refractory MM requiring current treatment.

               2. Previously failed ≥ 3 prior regimens.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1.

          -  Estimated life expectancy ≥ 4 months.

          -  No other medical, surgical, or psychiatric condition (including active substance
             abuse) that would interfere with compliance to the protocol, as determined by the
             Principal Investigator.

          -  Female subjects of childbearing potential must agree to use dual methods of
             contraception and have a negative serum pregnancy test at Screening, and male subjects
             must use an effective barrier method of contraception if sexually active with a female
             of childbearing potential.

          -  Subjects need a functioning, central venous access in place for the administration of
             agenT-797.

        Exclusion Criteria:

          -  Pregnant or nursing women.

          -  Prior history of invasive malignancy.

          -  Subjects who had an allogeneic stem cell transplantation and are still on
             immunosuppressive medications or corticosteroids above physiological dose.

          -  New York Heart Association Class III or IV heart failure, unstable angina, or a
             history of recent myocardial infarction.

          -  Adverse events from prior anticancer therapy that have not resolved to NCI CTCAE Grade
             ≤ 1.

          -  Receiving any investigational products within 4 weeks or 5 half-lives of cell
             infusion.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of AEs
Time Frame:Up to day 28 post cell infusion.
Safety Issue:
Description:Number of participants with treatment-related AEs as determined per NIC CTCAE v5.0

Secondary Outcome Measures

Measure:Persistence of allogeneic iNKT cells.
Time Frame:Baseline, 2 hours post cell infusion, and on Days 2, 3, 5, 8, 15, 22, and 29, Weeks 6, 8, and 12, and Months 6, 9, and 12.
Safety Issue:
Description:Persistence of agenT-797 in peripheral blood (SNP-based assay)
Measure:Clinical response evaluation.
Time Frame:End of study visit (up to 12 months).
Safety Issue:
Description:Evaluation using the International Myeloma Working Group (IMWG) consensus criteria.
Measure:Evaluation of immune response to donor cells
Time Frame:Baseline, Day 22, Week 6 and end of study visit (up to 12 months).
Safety Issue:
Description:Measurement of serum alloantibodies to MHC Class I and II

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AgenTus Therapeutics, Inc.

Trial Keywords

  • Multiple myeloma

Last Updated

February 15, 2021