AB-101 as Monotherapy and With Immunotherapy in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

February 9, 2024 updated by: Artiva Biotherapeutics, Inc.

A Multi-Center, Open-Label, Phase 1/2 Clinical Trial to Evaluate the Safety and Anti-Tumor Activity of AB-101 Monotherapy and AB-101 With Immunotherapy in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma of B-Cell Origin.

AB-101 is an off-the shelf, allogeneic cell product made of "natural killer" cells, also called NK cells. White blood cells are part of the immune system and NK cells are a type of white blood cell that are known to kill cancer cells.

This clinical trial will enroll patients with relapsed/refractory non-Hodgkin lymphoma of B-cell origin and is conducted in two phases. The primary objectives of Phase 1 are as follows: 1) to evaluate the safety of AB-101 given alone or in combination with rituximab (including the DLBCL specific cohort) or in combination with bendamustine and rituximab; 2) to evaluate the potential clinical activity of AB-101 when given in combination with rituximab or in combination with bendamustine and rituximab (combination cohorts only); and 3) to identify the recommended Phase 2 dose (RP2D). The primary objective of Phase 2 is to determine whether AB-101 in combination with rituximab or in combination with bendamustine and rituximab has anti-cancer activity in patients.

Patients will be assigned to receive either AB-101 alone as monotherapy, in combination with rituximab (including DLBCL specific cohort) or in combination with bendamustine and rituximab. All patients will receive at least 1 treatment cycle of AB-101, followed by scheduled assessments of overall health and tumor response. Patients receiving AB-101 in combination with rituximab may receive up to 3 additional cycles of treatment. Patients receiving AB-101 in combination with bendamustine and rituximab may receive up to 5 additional cycles of treatment. Patients enrolled into the DLBCL specific cohort receiving AB-101 in combination with rituximab may receive up to 3 cycles of treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

108

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35249
        • Recruiting
        • University of Alabama
        • Contact:
    • Arizona
      • Tucson, Arizona, United States, 85719
        • Recruiting
        • The University of Arizona Cancer Center - North Clinic
        • Contact:
        • Principal Investigator:
          • Abhijeet Kumar, MD
    • California
      • Orange, California, United States, 92868
        • Completed
        • University of California, Irvine
      • San Diego, California, United States, 92093
        • Recruiting
        • University of California San Diego Moores Cancer Center
        • Contact:
        • Principal Investigator:
          • Ayad Hamdan, M.D.
    • Florida
      • Gainesville, Florida, United States, 32608
        • Recruiting
        • UF Health Shands Cancer Hospital
        • Contact:
          • Emma Hall Rosenau, BB(ASCP) SBB, MPH, CCRP
          • Phone Number: 352-294-8938
          • Email: roseeg@ufl.edu
        • Principal Investigator:
          • Erin Dean, MD
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Blood and Marrow Transplant Group of Georgia at Northside Hospital
        • Principal Investigator:
          • Lawrence E Morris, Jr, MD
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • Rush University Medical Center
        • Contact:
        • Principal Investigator:
          • Sunita Nathan, MD
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa Hospitals and Clinics
        • Principal Investigator:
          • Umar Farooq, MD
        • Contact:
    • Kansas
    • Kentucky
      • Louisville, Kentucky, United States, 40241
        • Recruiting
        • Norton Cancer Institute
        • Contact:
        • Principal Investigator:
          • Joseph Maly, M.D.
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Karmanos Cancer Institute
        • Principal Investigator:
          • Dipenkumar Modi, MD
        • Contact:
    • New York
      • Lake Success, New York, United States, 11042
        • Recruiting
        • Northwell Health/R. J. Zuckerberg Cancer Center
        • Contact:
        • Principal Investigator:
          • Ruthee-Lu Bayer, MD
      • New York, New York, United States, 11021
        • Withdrawn
        • Weill Cornell Medicine
    • Ohio
      • Columbus, Ohio, United States, 43214
        • Recruiting
        • OhioHealth Research Institute
        • Contact:
        • Principal Investigator:
          • Basem William, MD
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health Sciences Center
        • Contact:
          • OHSU Clinical Trials Information Line
          • Phone Number: 503-494-1080
          • Email: trials@ohsu.edu
        • Principal Investigator:
          • Jennifer Saultz, D.O.
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Recruiting
        • Fox Chase Cancer Center
        • Contact:
        • Principal Investigator:
          • Rashmi Khanal, M.D.
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Jefferson Health
        • Principal Investigator:
          • Usama Gergis, MD
        • Contact:
          • Natisha Muhmmad, MPH, CCRP
          • Phone Number: 215-955-5769
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Rhode Island Hospital
        • Contact:
        • Principal Investigator:
          • Adam Olszewski, MD
    • Texas
      • Dallas, Texas, United States, 75246
        • Recruiting
        • Texas Oncology - Baylor Charles A. Sammons Cancer Center
        • Principal Investigator:
          • Houston Holmes, MD
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute, University of Utah
        • Contact:
        • Principal Investigator:
          • Boyu Hu, MD
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University
        • Principal Investigator:
          • Victor Yazbeck
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Confirmed diagnosis of aggressive NHL of B-cell origin. For enrollment into the DLBCL specific cohort: DLBCL, High-grade B-cell Lymphoma or PMBCL.
  • Patient must have progressed or demonstrated intolerance to at least two lines of FDA-approved therapies, one of which must have included anti-CD20 monoclonal antibody therapy. The following are permitted: Prior autologous hematopoietic stem cell transplantation, prior treatment with FDA-approved CAR-T therapy, and/or prior treatment with an investigational agent. Prior treatment(s) with an FDA-approved CAR-T cell therapy or other cell therapies is permitted as long the patients are not considered to be refractory to this previous cell therapy approach (defined as progression within 120 days from the infusion of the cell therapy approach).
  • Patient must have disease that allows for response assessment using the Lugano classification criteria.
  • Ability to understand and sign the ICF.

Exclusion Criteria:

  • Active CNS lymphoma or CNS involvement unless there is a history of at least 3 months of sustained remission of treated disease.
  • History of clinically significant structural cardiac disease.
  • Cardiac ejection fraction of < 45% on echocardiogram or MUGA scan at screening assessment.
  • Inadequate pulmonary function.
  • History of a solid organ allograft, or an inflammatory or autoimmune disease likely to be exacerbated by IL-2.
  • Ongoing uncontrolled systemic infections.
  • Positive HIV PCR test
  • Positive for Hepatitis B or Hepatitis C
  • Prior allogeneic stem cell transplant.
  • Females of childbearing potential must be willing and able to use appropriate contraception for duration of trial and for 6 months following final AB-101 dose. Males must be sterile or commit to using appropriate contraception until 90 days following the final dose of AB-101.
  • Individuals who are pregnant or lactating are ineligible.
  • Patients who received a previous genetically modified cell therapy product (e.g., CD19 CAR-T), and progressed within 120 days from the time of the cell therapy infusion

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD
Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD
Drug: AB-101
NK cell therapy
Drug: Rituximab
Anti-CD20 antibody therapy
Drug: Interleukin-2
Immune cytokine
Drug: Cyclophosphamide
Lymphodepleting chemotherapy
Drug: Fludarabine
Lymphodepleting chemotherapy
Drug: Bendamustine
Chemoimmunotherapy
Experimental: Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo
Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab
Drug: AB-101
NK cell therapy
Drug: Rituximab
Anti-CD20 antibody therapy
Drug: Interleukin-2
Immune cytokine
Drug: Cyclophosphamide
Lymphodepleting chemotherapy
Drug: Fludarabine
Lymphodepleting chemotherapy
Drug: Bendamustine
Chemoimmunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1, combination therapy: AB-101 clinical activity, determined by ORR
Time Frame: From baseline disease assessment through end of study participation.
Objective response rate (ORR) is defined as the proportion of patients with a documented complete response or partial response (CR + PR) in the absence of earlier disease progression.
From baseline disease assessment through end of study participation.
Phase 1, combination therapy: Identify the recommended Phase 2 dose (R2PD) for AB-101.
Time Frame: From ICF signature through 13 weeks after last study drug dose.
R2PD will be determined based on safety and tolerability of AB-101 in combination with rituximab or in combination with bendamustine and rituximab.
From ICF signature through 13 weeks after last study drug dose.
Phase 2: Determine the efficacy profile of AB-101 in combination with rituximab or in combination with bendamustine and rituximab when administered to patients with R/R NHL of B-cell origin.
Time Frame: From baseline disease assessment through end of study participation.
The efficacy profile will be determined by the ORR.
From baseline disease assessment through end of study participation.
Phase 1: Safety and tolerability of AB-101 as monotherapy, and in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab.
Time Frame: From the ICF signature through 13 weeks after last study drug dose.
Based on incidence, severity, and dose relationship of AEs and serious AEs (SAEs)
From the ICF signature through 13 weeks after last study drug dose.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Artiva Biotherapeutics, Inc.

Investigators

  • Study Director: Thorsten Graef, M.D., Ph.D., Artiva Biotherapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2021

Primary Completion (Estimated)

November 1, 2024

Study Completion (Estimated)

November 1, 2024

Study Registration Dates

First Submitted

December 4, 2020

First Submitted That Met QC Criteria

December 16, 2020

First Posted (Actual)

December 17, 2020

Study Record Updates

Last Update Posted (Estimated)

February 13, 2024

Last Update Submitted That Met QC Criteria

February 9, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AB-101-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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