Clinical trial NCT03189836: Study of ACTR707 in Combination With Rituximab in Subjects With Relapsed or Refractory B Cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lymphoma
Keywords: CD20+
B cell
ACTR
ACTR707
relapsed
refractory
T cell
T cell product
adoptive T cells
gene therapy
Lead sponsor: Cogent Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2017-06-16
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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)
* 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

Primary outcomes:
measure: Safety as assessed by dose limiting toxicities (DLTs)
timeFrame: 28 days
measure: Determination of maximum tolerated dose and proposed recommended Phase 2 dose
timeFrame: 24 weeks
Secondary outcomes:
measure: Anti-lymphoma activity as measured by overall response rate
timeFrame: 24 weeks
measure: Anti-lymphoma activity as measured by duration of response
timeFrame: 24 weeks
measure: Anti-lymphoma activity as measured by progression-free survival
timeFrame: 24 weeks
measure: Anti-lymphoma activity as measure by overall survival
timeFrame: 24 weeks
measure: Assessment of persistence of ACTR707 as measured by flow cytometry and qPCR
timeFrame: 24 weeks
measure: Assessment of ACTR707 phenotype and function as measured by flow cytometry
timeFrame: 24 weeks
measure: Assessment of inflammatory markers and cytokines/chemokines
timeFrame: 24 weeks
measure: Rituximab PK
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Emory University, Winship Cancer Institute
state: Georgia
city: Maywood
country: United States
facility: Loyola University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Bone and Marrow Transplantation
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Nashville
country: United States
facility: Tennessee Oncology - Nashville
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Cogent Biosciences, Inc.
name: Jessica Sachs, MD
role: STUDY_DIRECTOR
References:
citation: 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.