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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: ACTR087
* Biological: rituximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACTR087, in combination with rituximab<br> | Biological: ACTR087<br> <br> Biological: rituximab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as assessed by dose limiting toxicities (DLTs) |  | 28 days | 
| Safety as assessed by determination of the maximum tolerated dose (MTD) |  | 24 months | 
| Safety as assessed by determination of the recommended phase 2 dose (RP2D) |  | 24 months | 
| Safety as assessed by and adverse events, laboratory assessments and physical examinations |  | 24 months | 
| Safety as assessed by mini-mental state examination (MMSE) |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | 24 months | 
| Duration of response |  | 24 months | 
| Progression free survival |  | 24 months | 
| Overall survival |  | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD20+, B-cell, ACTR087, Relapsed, Refractory