Study of ACTR707 in Combination With Rituximab in Subjects With Relapsed or Refractory B Cell Lymphoma

Study Overview
=================
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.

Official Title
-----------------
Phase 1 Study of ACTR707, an Autologous T Cell Product, in Combination With Rituximab, in Subjects With Relapsed or Refractory CD20+ B Cell Lymphoma

Conditions
-----------------
Lymphoma

Intervention / Treatment
-----------------
* Biological: ACTR707
* Biological: rituximab


Participation Criteria
=================
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 (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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACTR707 in combination with rituximab<br> | Biological: ACTR707<br>* autologous T cell product<br>Biological: rituximab<br>* CD20-directed cytolytic antibody<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as assessed by dose limiting toxicities (DLTs) | Dose-limiting toxicities, MTD, incidence and severity of AEs and clinically significant abnormalities of laboratory values | 28 days | 
| Determination of maximum tolerated dose and proposed recommended Phase 2 dose |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-lymphoma activity as measured by overall response rate |  | 24 weeks | 
| Anti-lymphoma activity as measured by duration of response |  | 24 weeks | 
| 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 | 
| Assessment of ACTR707 phenotype and function as measured by flow cytometry |  | 24 weeks | 
| Assessment of inflammatory markers and cytokines/chemokines | Cytokines and Inflammatory markers | 24 weeks | 
| Rituximab PK | Rituximab plasma concentration | 24 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CD20+, B cell, ACTR, ACTR707, relapsed, refractory, T cell, T cell product, adoptive T cells, gene therapy