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

Cogent Biosciences, Inc.11 sites in 1 country26 target enrollmentOctober 4, 2017

ConditionsLymphoma

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Lymphoma
Sponsor: Cogent Biosciences, Inc.
Enrollment: 26
Locations: 11
Primary Endpoint: Safety as assessed by dose limiting toxicities (DLTs)
Status: Terminated
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 4, 2017

End Date

September 21, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Cogent Biosciences, Inc.

Responsible Party

Sponsor

Eligibility Criteria

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)

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

Outcomes

Primary Outcomes

Safety as assessed by dose limiting toxicities (DLTs)

Time Frame: 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

Time Frame: 24 weeks

Secondary Outcomes

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)
Rituximab PK(24 weeks)