Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

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

Protocol: OSU-15254

Full Title

Phase 1 Study of ACTR087, Autologous T Lymphocytes Expressing Antibody Coupled T-cell Receptors (CD16V-41BB-CD3ζ), in Combination with Rituximab, in Subjects with Relapsed or Refractory CD20-Positive B-Cell Lymphoma

Purpose

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.

Are you eligible?

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

Lymphoma