A Study to Evaluate the Safety and Preliminary Efficacy of ATA3219 in Participants With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

February 5, 2024 updated by: Atara Biotherapeutics

A Phase 1 Study to Evaluate the Safety and Preliminary Efficacy of ATA3219, Allogeneic Anti-CD19 Chimeric Antigen Receptor T-cell Therapy, in Subjects With Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

The purpose of this study is to evaluate the safety and preliminary efficacy of ATA3219 in participants with relapsed/refractory (R/R) B-cell non-Hodgkin Lymphoma (NHL).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1, open-labeled study to evaluate the safety and preliminary efficacy of ATA3219 (as monotherapy) in participants with NHL. During dose escalation, participants with R/R large B-cell lymphoma (LBCL), follicular lymphoma (FL), or mantle cell lymphoma (MCL) may be enrolled sequentially. Up to 4 dose levels will be explored in dose escalation. Prior to undergoing any screening procedure, prospective participants must undergo the ATA3219 inventory check assessments to ensure availability of an appropriate partially human leukocyte antigen-matched ATA3219 lot. Before administration of ATA3219, participants will receive conditioning chemotherapy. Participants will be hospitalized for at least 1 week to receive ATA3219, which will be administered by intravenous (IV) infusion on Day 1 in a staggered manner to allow appropriate safety monitoring. Four different dose levels will be studied in a sequential manner, and a lower dose level may be added, if needed. At least 3 and up to 6 dose-limiting toxicity (DLT)-evaluable participants, those who complete the 28-day DLT observation period, will be assessed at each dose level. Disease response will be assessed on Day 28 (± 5 days) following each dose of ATA3219 by the investigator using the Lugano criteria (Cheson 2014). Participants who achieve complete response (CR) or progressive disease at Day 28 will enter the 24-month follow-up period.

After recommended phase 2 dose (RP2D) has been determined in the dose escalation stage, additional participants may be enrolled in 2 expansion cohorts (CD19-directed naive and prior CD19-directed therapy), opened at sponsor discretion and dosed at the proposed RP2D.

After treatment is completed or discontinued, participants will be followed for response and safety for up to 24 months from the last dose of ATA3219. After 2 years, a separate long-term follow-up study will be conducted to follow participants for up to 15 years.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed, R/R, B-cell NHL according to the 2022 revision of the World Health Organization classification of lymphoid neoplasms [Alaggio 2022] defined as any of the following:

    1. LBCL
    2. FL Grade 3b
    3. MCL
  • The following criteria apply for details of prior treatment/therapy: R/R to at least 2 lines of therapy; if the most recent line of therapy was autologous hematologic cell transplant (HCT), relapse within 12 months of the transplant.
  • Measurable disease by scan (diagnostic positron emission tomography-positive and/or computed tomography-measurable) as per Lugano Classification [Cheson 2014]. Magnetic resonance imaging may be used when computed tomography with contrast is contraindicated or when mandated by local practice.
  • If sufficient archival material is not available from the latest relapse, a new tumor biopsy is required any time during screening, prior to conditioning chemotherapy.

  • Participants with LBCL who have received prior CD19-directed therapy as the prior line of therapy:

    1. must have achieved either a CR or partial response as a best response and maintained the response for ≥ 3 months after receiving CD19-directed treatment, and
    2. must still have CD19+ disease as determined by a local laboratory.
  • Eastern Cooperative Oncology Group performance status ≤ 1
  • Adequate organ function
  • Written informed consent as per protocol.
  • Participants are able to commit to the inpatient portion of the study, encompassing conditioning (if per the institution's standard practice), and frequent monitoring during Days 1-15, as well as remain within 1 hour travel time of the clinical site for 28 days after each infusion.

Exclusion Criteria:

  • History of a human immunodeficiency virus infection or acute or chronic active hepatitis B or C infection.
  • History or presence of clinically relevant central nervous system pathology.
  • Unresolved Grade 1-2 Immune effector cell-associated neurotoxicity syndrome (ICANS) or experienced Grade 3-4 ICANS from prior chimeric antigen receptor T-cell.
  • Unresolved graft-versus-host disease (GvHD) or Grade 3-4 acute GvHD from any prior therapy or moderate to severe chronic GvHD from any prior therapy.
  • History of any one of the following cardiovascular conditions: class III or IV heart failure as defined by the New York Heart Association [The Criteria Committee of the New York Heart Association 1994], cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically meaningful cardiac disease, within the past 6 months of study informed consent.
  • History of malignancies, other than R/R NHL, unless the participant has been disease-free for ≥ 2 years (certain noninvasive malignancies are allowed).
  • Active primary/CNS-only involvement by lymphoma, unless the CNS involvement has been effectively treated.
  • Active autoimmune disorders or inflammatory conditions that require systemic immunosuppressive therapies, including therapeutic doses of steroids.
  • Has received prior allogeneic HCT or prior solid organ transplant.
  • Systemic bacterial, viral, fungal, or other infection that is untreated or unresponsive to appropriate treatment (or requires IV antibiotics at enrollment); participants must be afebrile for ≥ 48 hours. Prophylactic antibiotics, antivirals, and antifungals are permitted.
  • Concurrent serious uncontrolled or unresolved medical condition, including any laboratory abnormality or psychiatric illness.
  • For participants with MCL or FL, any prior CD19-directed therapy.
  • The following therapies within defined periods prior to the conditioning regimen: therapeutic doses of corticosteroids (> 0.5 mg/kg/day of prednisone or equivalent), lymphodepleting chemotherapeutic agents, live attenuated vaccines, prior systemic cancer therapy, investigational agents, including approved drugs being used off label, autologous HCT, donor lymphocyte infusions, radiation, alemtuzumab.
  • Female who is breastfeeding or pregnant.
  • Inability or unwillingness to comply with study procedures.
  • Unwilling to use protocol specified contraceptive methods

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ATA3219 Dose Level 1
Participants will receive a single IV infusion of ATA3219 Dose Level 1 on Day 1.
Drug: ATA3219
ATA3219 is allogeneic anti-CD19 chimeric antigen receptor T-cell, administered intravenously on Day 1.
Experimental: ATA3219 Dose Level 2
Participants will receive a single IV infusion of ATA3219 Dose Level 2 on Day 1.
Drug: ATA3219
ATA3219 is allogeneic anti-CD19 chimeric antigen receptor T-cell, administered intravenously on Day 1.
Experimental: ATA3219 Dose Level 3
Participants will receive a single IV infusion of ATA3219 Dose Level 3 on Day 1.
Drug: ATA3219
ATA3219 is allogeneic anti-CD19 chimeric antigen receptor T-cell, administered intravenously on Day 1.
Experimental: ATA3219 Dose Level 4
Participants will receive a single IV infusion of ATA3219 Dose Level 4 on Day 1.
Drug: ATA3219
ATA3219 is allogeneic anti-CD19 chimeric antigen receptor T-cell, administered intravenously on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence and Severity of Treatment-emergent Adverse Events (TEAEs)
Time Frame: Day 1 through 90 days after the last dose of study drug
Day 1 through 90 days after the last dose of study drug
Incidence and Severity of Adverse Events of Special Interest (AESIs)
Time Frame: Day 1 through 90 days after the last dose of study drug
Day 1 through 90 days after the last dose of study drug
Clinically Significant Changes in Laboratory Parameters
Time Frame: Day 1 through 90 days after the last dose of study drug
Day 1 through 90 days after the last dose of study drug
Incidence of Dose-limiting Toxicities (DLTs)
Time Frame: Day 1 through Day 28 of first dose
Day 1 through Day 28 of first dose
Maximum Tolerated dose (MTD)
Time Frame: Day 1 through Day 28 of first dose
Day 1 through Day 28 of first dose
Recommended Phase 2 Dose (RP2D)
Time Frame: Day 1 through Day 28 of first dose
Day 1 through Day 28 of first dose

Secondary Outcome Measures

Outcome Measure
Time Frame
Maximum Observed Plasma Concentration (Cmax) of ATA3219
Time Frame: Pre-dose Day 1 through 24 months after last dose on a defined schedule
Pre-dose Day 1 through 24 months after last dose on a defined schedule
Time to Reach Cmax of ATA3219
Time Frame: Pre-dose Day 1 through 24 months after last dose on a defined schedule
Pre-dose Day 1 through 24 months after last dose on a defined schedule
Partial Area Under the Curve (pAUC) of ATA3219
Time Frame: Pre-dose Day 1 through 24 months after last dose on a defined schedule
Pre-dose Day 1 through 24 months after last dose on a defined schedule
Last Observed Plasma Concentration (Clast) of ATA3219
Time Frame: Pre-dose Day 1 through 24 months after last dose on a defined schedule
Pre-dose Day 1 through 24 months after last dose on a defined schedule
Time of Clast of ATA3219
Time Frame: Pre-dose Day 1 through 24 months after last dose on a defined schedule
Pre-dose Day 1 through 24 months after last dose on a defined schedule
Terminal Half-life (T1/2) of ATA3219
Time Frame: Pre-dose Day 1 through 24 months after last dose on a defined schedule
Pre-dose Day 1 through 24 months after last dose on a defined schedule
Objective Response Rate (ORR)
Time Frame: Screening (≤ 28 days before enrollment) through 24 months after last dose
Screening (≤ 28 days before enrollment) through 24 months after last dose
Complete Response Rate (CRR)
Time Frame: Screening (≤ 28 days before enrollment) through 24 months after last dose
Screening (≤ 28 days before enrollment) through 24 months after last dose
Time-to-response (TTR)
Time Frame: Screening (≤ 28 days before enrollment) through 24 months after last dose
Screening (≤ 28 days before enrollment) through 24 months after last dose
Duration of Response (DOR)
Time Frame: Screening (≤ 28 days before enrollment) through 24 months after last dose
Screening (≤ 28 days before enrollment) through 24 months after last dose
Progression-free Survival (PFS)
Time Frame: Screening (≤ 28 days before enrollment) through 24 months after last dose
Screening (≤ 28 days before enrollment) through 24 months after last dose
Overall Survival (OS)
Time Frame: Screening (≤ 28 days before enrollment) through 24 months after last dose
Screening (≤ 28 days before enrollment) through 24 months after last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Atara Biotherapeutics

Investigators

  • Study Director: Aditi Mehta, DO, Atara Biotherapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 22, 2024

Primary Completion (Estimated)

May 1, 2026

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

February 5, 2024

First Submitted That Met QC Criteria

February 5, 2024

First Posted (Estimated)

February 13, 2024

Study Record Updates

Last Update Posted (Estimated)

February 13, 2024

Last Update Submitted That Met QC Criteria

February 5, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ATA3219-NHL-103

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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