Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

AGENT-797 in Patients With Relapsed/Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04754100
Recruitment Status : Recruiting
First Posted : February 15, 2021
Last Update Posted : May 6, 2021
Sponsor:
Information provided by (Responsible Party):
Agenus Inc. ( AgenTus Therapeutics, Inc. )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Multiple Myeloma Drug: agenT-797 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 29, 2021
Estimated Primary Completion Date : April 15, 2022
Estimated Study Completion Date : April 15, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Dosage and Cohorts

Part 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.

Drug: agenT-797

Part 1 agenT-797 is an off-the shelf cell therapy consisting of ≥ 95% allogeneic human unmodified iNKT isolated from 1 healthy donor mononuclear cell apheresis unit and expanded ex-vivo.

Part 2 agenT-797 is an off-the shelf cell therapy consisting of ≥ 95% allogeneic human unmodified iNKT isolated from 1 healthy donor mononuclear cell apheresis unit and expanded ex-vivo.

Lymphodepletion:

The conditioning therapy will be administered prior to agenT-797 infusion. Dose and rate of infusion of the chemotherapy may be adapted as medically indicated.





Primary Outcome Measures :
  1. Incidence of AEs [ Time Frame: Up to day 28 post cell infusion. ]
    Number of participants with treatment-related AEs as determined per NIC CTCAE v5.0

  2. Correlation of the dose of iNKT cell therapy with the incidence, nature, and intensity of AEs. [ Time Frame: Up to day 28 post cell infusion. ]
    Evaluation of AEs at each dose level.

  3. Recommended Phase 2 dose [ Time Frame: 28 days post cell infusion ]
    Maximum Tolerated Dose (MTD) based on DLT occurence at DLT period (28 days after cell infusion).


Secondary Outcome Measures :
  1. 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. ]
    Persistence of agenT-797 in peripheral blood (SNP-based assay)

  2. Clinical response evaluation. [ Time Frame: End of study visit (up to 12 months). ]
    Evaluation using the International Myeloma Working Group (IMWG) consensus criteria.

  3. Evaluation of immune response to donor cells [ Time Frame: Baseline, Day 22, Week 6 and end of study visit (up to 12 months). ]
    Measurement of serum alloantibodies to MHC Class I and II



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT04754100


Contacts
Layout table for location contacts
Contact: Agenus, Inc. Clinical Trial Information 781-674-4265 clinicaltrialinfo@agenusbio.com

Locations
Layout table for location information
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Clifton Mo, MD       Clifton_Mo@DFCI.HARVARD.EDU   
Principal Investigator: Clifton Mo, MD         
Sponsors and Collaborators
AgenTus Therapeutics, Inc.
Investigators
Layout table for investigator information
Study Director: Medical Director AgenTus Therapeutics, Inc.
Layout table for additonal information
Responsible Party: AgenTus Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04754100    
Other Study ID Numbers: 2019-1305
First Posted: February 15, 2021    Key Record Dates
Last Update Posted: May 6, 2021
Last Verified: May 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Agenus Inc. ( AgenTus Therapeutics, Inc. ):
Multiple myeloma
Additional relevant MeSH terms:
Layout table for MeSH terms
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