Study of ACTR707 in Combination With Rituximab in Subjects With Relapsed or Refractory B Cell Lymphoma

Phase 1 Study of ACTR707, an Autologous T Cell Product, in Combination With Rituximab, in Subjects With Relapsed or Refractory CD20+ B Cell Lymphoma

This is a phase 1, multi-center, single-arm, open-label study evaluating the safety and anti-lymphoma activity of an autologous T cell product (ACTR707) in combination with rituximab in subjects with refractory or relapsed CD20+ B cell lymphoma.

Study Overview

• Status: Terminated
• Conditions: Lymphoma
• Intervention / Treatment: Biological: ACTR707; Biological: rituximab

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University, Winship Cancer Institute
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University
  • Indiana
    • Indianapolis, Indiana, United States, 46327
      • Indiana Bone and Marrow Transplantation
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology - Nashville
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• signed written informed consent obtained prior to study procedures
• histologically-confirmed relapsed or refractory CD20+ B-cell lymphoma of one of the following types, with documented disease progression or recurrence following the immediate prior therapy: DLBCL (regardless of cell of origin or underlying molecular genetics), MCL, PMBCL, Gr3b-FL, TH-FL (prior dx of FL before transforming to DLBCL).
• biopsy-confirmed CD20+ expression of the underlying malignancy with disease progression following immediate prior therapy
• at least 1 measurable lesion on imaging.

• must have received adequate prior therapy for the underlying CD20+ B-cell lymphoma, defined as an anti-CD20 mAb in combination with an anthracycline-containing chemotherapy regimen (i.e. chemo-immunotherapy) and at least one of the following:

  • biopsy-proven refractory disease after frontline chemo-immunotherapy
  • relapse within 1 year from frontline chemo-immunotherapy and ineligible for autologous hematopoietic stem cell transplant (auto-HSCT)
  • for subjects with DLBCL, PMBCL, and Gr3b-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT
  • for subjects with TH-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT. At least 1 prior regimen with an anti-CD20 mAb in combination with chemotherapy is required following documented transformation
  • for subjects with MCL (confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization (FISH) or polymerase chain reaction (PCR): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-HSCT is allowable)
• ECOG 0 or 1
• life expectancy of at least 6 months
• platelet count greater than 50,000/µL

Exclusion Criteria:

• known active central nervous system (CNS) involvement by malignancy.

• prior treatment as follows:

  • alemtuzumab within 6 months of enrollment
  • fludarabine, cladribine, or clofarabine within 3 months of enrollment
  • external beam radiation within 2 weeks of enrollment
  • mAb (including rituximab) within 2 weeks of enrollment
  • other lymphotoxic chemotherapy (including steroids except as below) within 2 weeks of enrollment
  • experimental agents within 3 half-lives prior to enrollment, unless progression is documented on therapy
• clinically significant cardiac disease
• clinically significant active infection
• clinically significant CNS disorder
• clinical history, prior diagnosis, or overt evidence of autoimmune disease
• known bone marrow involvement due to underlying malignant disease, in dose-escalation phase only

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACTR707 in combination with rituximab	Biological: ACTR707; autologous T cell product; Biological: rituximab; CD20-directed cytolytic antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety as assessed by dose limiting toxicities (DLTs)	Dose-limiting toxicities, MTD, incidence and severity of AEs and clinically significant abnormalities of laboratory values	28 days
Determination of maximum tolerated dose and proposed recommended Phase 2 dose		24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-lymphoma activity as measured by overall response rate		24 weeks
Anti-lymphoma activity as measured by duration of response		24 weeks
Anti-lymphoma activity as measured by progression-free survival		24 weeks
Anti-lymphoma activity as measure by overall survival		24 weeks
Assessment of persistence of ACTR707 as measured by flow cytometry and qPCR		24 weeks
Assessment of ACTR707 phenotype and function as measured by flow cytometry		24 weeks
Assessment of inflammatory markers and cytokines/chemokines	Cytokines and Inflammatory markers	24 weeks
Rituximab PK	Rituximab plasma concentration	24 weeks

Collaborators and Investigators

• Sponsor: Cogent Biosciences, Inc.

Publications and helpful links

General Publications

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2017
• Primary Completion (Actual): September 21, 2020
• Study Completion (Actual): September 21, 2020

Study Registration Dates

• First Submitted: June 12, 2017
• First Submitted That Met QC Criteria: June 14, 2017
• First Posted (Actual): June 16, 2017

Study Record Updates

• Last Update Posted (Actual): October 11, 2021
• Last Update Submitted That Met QC Criteria: October 4, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: gene therapy; relapsed; refractory; T cell; B cell; CD20+; ACTR; T cell product; adoptive T cells; ACTR707
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: ATTCK-20-03

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