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

Phase 1

Terminated

• Conditions: Lymphoma
• Interventions: Biological: ACTR707; Biological: rituximab

• Registration Number: NCT03189836
• Lead Sponsor: Cogent Biosciences, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-06-12
• Study First Submitted QC: 2017-06-14
• Study First Posted: 2017-06-16
• Study Start: 2017-10-04
• Primary Completion: 2020-09-21
• Study Completion: 2020-09-21
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-04
• Last Update Posted: 2021-10-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 26

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ACTR707 in combination with rituximab	ACTR707	-
ACTR707 in combination with rituximab	rituximab	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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
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 inflammatory markers and cytokines/chemokines	24 weeks	Cytokines and Inflammatory markers
Rituximab PK	24 weeks	Rituximab plasma concentration

Trial Locations

Locations (11)

Yale University; 🇺🇸 New Haven, Connecticut, United States

Emory University, Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Loyola University; 🇺🇸 Maywood, Illinois, United States

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

Indiana Bone and Marrow Transplantation; 🇺🇸 Indianapolis, Indiana, United States

University of Maryland; 🇺🇸 Baltimore, Maryland, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Tennessee Oncology - Nashville; 🇺🇸 Nashville, Tennessee, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States