Lymphoma
Conditions
Keywords
CD20+, B cell, ACTR, ACTR707, relapsed, refractory, T cell, T cell product, adoptive T cells, gene therapy
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.
Interventions
BIOLOGICALACTR707
autologous T cell product
BIOLOGICALrituximab
CD20-directed cytolytic antibody
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 80 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 (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as assessed by dose limiting toxicities (DLTs) | 28 days | Dose-limiting toxicities, MTD, incidence and severity of AEs and clinically significant abnormalities of laboratory values |
| Determination of maximum tolerated dose and proposed recommended Phase 2 dose | 24 weeks | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-lymphoma activity as measured by progression-free survival | 24 weeks | — |
| Anti-lymphoma activity as measure by overall survival | 24 weeks | — |
| Assessment of persistence of ACTR707 as measured by flow cytometry and qPCR | 24 weeks | — |
| Anti-lymphoma activity as measured by overall response rate | 24 weeks | — |
| Assessment of inflammatory markers and cytokines/chemokines | 24 weeks | Cytokines and Inflammatory markers |
| Rituximab PK | 24 weeks | Rituximab plasma concentration |
| Assessment of ACTR707 phenotype and function as measured by flow cytometry | 24 weeks | — |
| Anti-lymphoma activity as measured by duration of response | 24 weeks | — |
Countries
United States
Outcome results
None listed