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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03189836
• Other study ID #: ATTCK-20-03
• Status: Terminated
• Phase: Phase 1
• Start date: October 4, 2017
• Est. completion date: September 21, 2020

Study information

• Verified date: October 2021
• Source: Cogent Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: September 21, 2020
• Est. primary completion date: September 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma

Intervention

Biological:
• ACTR707
autologous T cell product
• rituximab
CD20-directed cytolytic antibody

Locations

Country	Name	City	State
United States	Emory University, Winship Cancer Institute	Atlanta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	Ohio State University	Columbus	Ohio
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana Bone and Marrow Transplantation	Indianapolis	Indiana
United States	Loyola University	Maywood	Illinois
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Tennessee Oncology - Nashville	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Cogent Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Determination of maximum tolerated dose and proposed recommended Phase 2 dose		24 weeks
Secondary	Anti-lymphoma activity as measured by overall response rate		24 weeks
Secondary	Anti-lymphoma activity as measured by duration of response		24 weeks
Secondary	Anti-lymphoma activity as measured by progression-free survival		24 weeks
Secondary	Anti-lymphoma activity as measure by overall survival		24 weeks
Secondary	Assessment of persistence of ACTR707 as measured by flow cytometry and qPCR		24 weeks
Secondary	Assessment of ACTR707 phenotype and function as measured by flow cytometry		24 weeks
Secondary	Assessment of inflammatory markers and cytokines/chemokines	Cytokines and Inflammatory markers	24 weeks
Secondary	Rituximab PK	Rituximab plasma concentration	24 weeks