Study of ACTR087 in Subjects With Relapsed or Refractory B-cell Lymphoma

NCT ID: NCT02776813

Last Updated: 2020-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2020-02-12

Brief Summary

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

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ACTR087, in combination with rituximab

Group Type: EXPERIMENTAL

ACTR087

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

Interventions

ACTR087

Intervention Type: BIOLOGICAL

rituximab

Intervention Type: BIOLOGICAL

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
• Biopsy-confirmed CD20+ expression of the underlying malignancy by immunohistochemical staining or flow cytometry between the most recent dose of an anti-CD20 monoclonal antibody (mAb) and study enrollment
• At least 1 measurable lesion on imaging. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
• 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 PCR): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-HSCT is allowable)
• Karnofsky performance scale ≥ 60%
• Life expectancy of at least 6 months
• ANC > 1000/µL
• Platelet count > 50,000/µL
• For women of childbearing potential (defined as physiologically capable of becoming pregnant), agreement to use of highly effective contraception for at least 1 year following ACTR087 infusion. For men with partners of childbearing potential, agreement to use effective barrier contraception for at least 1 year following ACTR087 infusion

Exclusion Criteria

• Known active central nervous system (CNS) involvement by malignancy. Subjects with prior CNS involvement with their lymphoma must have completed effective treatment of their CNS disease at least 3 months prior to enrollment with no evidence of disease clinically and at least stable findings on relevant CNS imaging
• 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
• Serum creatinine ≥ 1.5 X age-adjusted upper limits of normal (ULN)
• Pulse oximetry < 92% on room air
• Direct bilirubin ≥ 3.0 mg/dL (50 mmol/L)
• Alanine transaminase (ALT) ≥ 3 times the ULN, unless determined to be directly due to lymphoma.
• Aspartate transaminase (AST) ≥ 3 times the ULN, unless determined to be directly due to lymphoma
• Class III or IV heart failure as defined by the New York Heart Association (NYHA), history of cardiac angioplasty or stenting, documented myocardial infarction or unstable angina within 6 months prior to enrollment, cardiac ejection fraction of < 45%, or other clinically significant cardiac disease
• Clinical history of, prior diagnosis of, or overt evidence of autoimmune disease, regardless of severity
• Clinically significant active infection, in the judgment of the investigator
• Pregnancy (negative serum pregnancy test to be obtained within 6 days prior to enrollment for subjects of childbearing potential)
• Breastfeeding
• Primary immunodeficiency
• Seropositive for Human Immunodeficiency Virus (HIV) 1 or HIV 2, or positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody
• Will need or has needed active treatment of a second malignancy within the prior 3 years before enrollment, other than FL, non-melanoma skin cancers, localized prostate cancer treated with curative intent, or cervical carcinoma in situ
• Is unable to receive any of the agents used in this study due a history of severe immediate hypersensitivity reaction (e.g. hypersensitivity to dimethyl sulfoxide (DMSO))
• History of prior allogeneic HSCT
• History of Richter's transformation from CLL
• Prior infusion of a genetically modified therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cogent Biosciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jessica Sachs, MD

Role: STUDY_DIRECTOR

Cogent Biosciences, Inc.

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Yale University

New Haven, Connecticut, United States

Loyola University Chicago

Maywood, Illinois, United States

Indiana Bone and Marrow Transplantation

Indianapolis, Indiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Duke University Medical Center

Durham, North Carolina, United States

Ohio State University

Columbus, Ohio, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34515338 (View on PubMed)

Other Identifiers

ATTCK-20-2

Identifier Type: OTHER

Identifier Source: secondary_id

UT-201501

Identifier Type: -

Identifier Source: org_study_id