Lymphoma
Conditions
Keywords
CD20+, B-cell, ACTR087, Relapsed, Refractory
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.
Interventions
BIOLOGICALACTR087
BIOLOGICALrituximab
Sponsors
Cogent Biosciences, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety as assessed by and adverse events, laboratory assessments and physical examinations | 24 months |
| 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 dose limiting toxicities (DLTs) | 28 days |
| Safety as assessed by mini-mental state examination (MMSE) | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Progression free survival | 24 months |
| Overall response rate | 24 months |
| Duration of response | 24 months |
| Overall survival | 60 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| ACRT087 persistence | 60 months | Blood samples will be collected and analyzed for the presence of T-cells which express antibody coupled T-cell receptors, using flow cytometry and qPCR |
| Rituximab serum concentrations | 147 days | — |
| Serum cytokine levels | 169 days | — |
| Serum inflammatory markers | 169 days | — |
Countries
United States
Outcome results
None listed