AB-101 as Monotherapy and With Immunotherapy in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma
- Conditions
- Non Hodgkin Lymphoma
- Interventions
- Registration Number
- NCT04673617
- Lead Sponsor
- Artiva Biotherapeutics, Inc.
- Brief Summary
AB-101 is an off-the shelf, allogeneic cell product made of "natural killer" cells, also called NK cells. White blood cells are part of the immune system and NK cells are a type of white blood cell that are known to kill cancer cells.
This clinical trial will enroll patients with relapsed/refractory non-Hodgkin lymphoma of B-cell origin and is conducted in two phases. The primary objectives of Phase 1 are as follows: 1) to evaluate the safety of AB-101 given alone or in combination with rituximab (including the DLBCL specific cohort) or in combination with bendamustine and rituximab; 2) to evaluate the potential clinical activity of AB-101 when given in combination with rituximab or in combination with bendamustine and rituximab (combination cohorts only); and 3) to identify the recommended Phase 2 dose (RP2D). The primary objective of Phase 2 is to determine whether AB-101 in combination with rituximab or in combination with bendamustine and rituximab has anti-cancer activity in patients.
Patients will be assigned to receive either AB-101 alone as monotherapy, in combination with rituximab (including DLBCL specific cohort) or in combination with bendamustine and rituximab. All patients will receive at least 1 treatment cycle of AB-101, followed by scheduled assessments of overall health and tumor response. Patients receiving AB-101 in combination with rituximab may receive up to 3 additional cycles of treatment. Patients receiving AB-101 in combination with bendamustine and rituximab may receive up to 5 additional cycles of treatment. Patients enrolled into the DLBCL specific cohort receiving AB-101 in combination with rituximab may receive up to 3 cycles of treatment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 108
- Confirmed diagnosis of aggressive NHL of B-cell origin. For enrollment into the DLBCL specific cohort: DLBCL, High-grade B-cell Lymphoma or PMBCL.
- Patient must have progressed or demonstrated intolerance to at least two lines of FDA-approved therapies, one of which must have included anti-CD20 monoclonal antibody therapy. The following are permitted: Prior autologous hematopoietic stem cell transplantation, prior treatment with FDA-approved CAR-T therapy, and/or prior treatment with an investigational agent. Prior treatment(s) with an FDA-approved CAR-T cell therapy or other cell therapies is permitted as long the patients are not considered to be refractory to this previous cell therapy approach (defined as progression within 120 days from the infusion of the cell therapy approach).
- Patient must have disease that allows for response assessment using the Lugano classification criteria.
- Ability to understand and sign the ICF.
- Active CNS lymphoma or CNS involvement unless there is a history of at least 3 months of sustained remission of treated disease.
- History of clinically significant structural cardiac disease.
- Cardiac ejection fraction of < 45% on echocardiogram or MUGA scan at screening assessment.
- Inadequate pulmonary function.
- History of a solid organ allograft, or an inflammatory or autoimmune disease likely to be exacerbated by IL-2.
- Ongoing uncontrolled systemic infections.
- Positive HIV PCR test
- Positive for Hepatitis B or Hepatitis C
- Prior allogeneic stem cell transplant.
- Females of childbearing potential must be willing and able to use appropriate contraception for duration of trial and for 6 months following final AB-101 dose. Males must be sterile or commit to using appropriate contraception until 90 days following the final dose of AB-101.
- Individuals who are pregnant or lactating are ineligible.
- Patients who received a previous genetically modified cell therapy product (e.g., CD19 CAR-T), and progressed within 120 days from the time of the cell therapy infusion
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD Cyclophosphamide Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD Fludarabine Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD Interleukin-2 Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo AB-101 Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo Interleukin-2 Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD AB-101 Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD Bendamustine Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo Rituximab Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo Cyclophosphamide Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab Phase 2: AB-101 given with rituximab or with BR to patients with B-cell NHL at the R2PD Rituximab Phase 2: AB-101 given with rituximab or with bendamustine and rituximab to patients with B-cell NHL at the R2PD Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo Fludarabine Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab Phase 1: Dose confirmation of AB-101 as mono, ritux combo (including DLBCL specific) & BR combo Bendamustine Phase 1: Dose confirmation of AB-101 as monotherapy, in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab
- Primary Outcome Measures
Name Time Method Phase 1: Safety and tolerability of AB-101 as monotherapy, and in combination with rituximab (including the DLBCL specific cohort) and in combination with bendamustine and rituximab. From the ICF signature through 13 weeks after last study drug dose. Based on incidence, severity, and dose relationship of AEs and serious AEs (SAEs)
Phase 1, combination therapy: AB-101 clinical activity, determined by ORR From baseline disease assessment through end of study participation. Objective response rate (ORR) is defined as the proportion of patients with a documented complete response or partial response (CR + PR) in the absence of earlier disease progression.
Phase 1, combination therapy: Identify the recommended Phase 2 dose (R2PD) for AB-101. From ICF signature through 13 weeks after last study drug dose. R2PD will be determined based on safety and tolerability of AB-101 in combination with rituximab or in combination with bendamustine and rituximab.
Phase 2: Determine the efficacy profile of AB-101 in combination with rituximab or in combination with bendamustine and rituximab when administered to patients with R/R NHL of B-cell origin. From baseline disease assessment through end of study participation. The efficacy profile will be determined by the ORR.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (21)
University of Alabama
🇺🇸Birmingham, Alabama, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
UF Health Shands Cancer Hospital
🇺🇸Gainesville, Florida, United States
Oregon Health Sciences Center
🇺🇸Portland, Oregon, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
Blood and Marrow Transplant Group of Georgia at Northside Hospital
🇺🇸Atlanta, Georgia, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Cancer Center of Kansas
🇺🇸Wichita, Kansas, United States
University of California, Irvine
🇺🇸Orange, California, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
The University of Arizona Cancer Center - North Clinic
🇺🇸Tucson, Arizona, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Northwell Health/R. J. Zuckerberg Cancer Center
🇺🇸Lake Success, New York, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of California San Diego Moores Cancer Center
🇺🇸San Diego, California, United States
OhioHealth Research Institute
🇺🇸Columbus, Ohio, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Huntsman Cancer Institute, University of Utah
🇺🇸Salt Lake City, Utah, United States
Jefferson Health
🇺🇸Philadelphia, Pennsylvania, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States