Preliminary Safety and Tolerability of CD19x22 CAR T Cells in Adolescent and Adult R/R B-NHL Patients

NCT05098613 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 21-2578.ccNCI-2021-11091
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label, single arm phase 1 trial aims to determine the safety and tolerability of anti-CD19 and anti-CD22 chimeric antigen receptor-expressing (CAR) T cells (CD19x22 CAR T) in adolescents and adults with relapsed/refractory (R/R) B-cell Non-Hodgkin Lymphoma (B-NHL). This trial will determine the maximum tolerated dose of CD19x22 CAR T cells using a standard 3+3 trial design.

Conditions

Non-Hodgkin Lymphoma; B-cell Non-Hodgkin Lymphoma (B-NHL); CNS Lymphoma; Mantle Cell Lymphoma (MCL)

Keywords

Relapsed; Refractory

Outcome Measures

Primary Outcomes (2)

• Overall safety and tolerability of CD19x22 CAR T Therapy in CAR-naive and CAR-treated subjects

  Assessed by Type, Frequency, and Severity of Adverse Events (AEs). All AEs, including laboratory abnormalities, will be graded using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grading criteria.

  12 Months Post Infusion

• Determine the Recommended Phase II Dose (RP2D) Level

  Incidence and frequency of Grade 3-5 toxicity occurring within the dose limiting toxicity (DLT) period post CD19x22 CAR T infusion. Grades 3-5 adverse events (AEs) are defined as Severe, Life-Threatening, and Fatal.

  30 Days Post Infusion

Secondary Outcomes (3)

• Feasibility of Manufacturing CD19x22 CAR T

  Day 0 (Infusion)

• Evaluate Safety of Infusion

  30 Days Post Infusion

• Evaluate Clinical Efficacy of CD19x22 CAR T

  12 Months Post Infusion

Study Arms (3)

Cohort 1 Relapsed/Refractory Non-CNS B-Cell Non Hodgkin Lymphoma

EXPERIMENTAL

Lymphodepleting chemotherapy followed by infusion of CD19x22 CAR T Cells starting at dose level 1.

Drug: CD19x22 CAR T Cells

Cohort 2 Relapsed/Refractory Mantle Cell Lymphoma

EXPERIMENTAL

Lymphodepleting chemotherapy followed by CD19x22 CART Infusion starting at dose level 2.

Drug: CD19x22 CAR T Cells

Cohort 3: Relapsed and/or Refractory Primary CNS Lymphoma OR secondary CNS Lymphoma

EXPERIMENTAL

Lymphodepleting chemotherapy followed by CD19x22 CAR T Infusion starting at dose level 2

Drug: CD19x22 CAR T Cells

Interventions

CD19x22 CAR T Cells DRUG

Autologous peripheral blood mononuclear cells transduced with CD19x22 CAR T lentiviral vector.

Cohort 1 Relapsed/Refractory Non-CNS B-Cell Non Hodgkin Lymphoma; Cohort 2 Relapsed/Refractory Mantle Cell Lymphoma; Cohort 3: Relapsed and/or Refractory Primary CNS Lymphoma OR secondary CNS Lymphoma

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age: ≥ 16 years of age with no upper age limit. (NOTE: the first three subjects on this trial must be ≥ 18 years of age.)
• COHORT 1: Non-CNS B-NHL
• Histologically confirmed aggressive B-cell NHL including the following types defined by World Health Organization (WHO) 2008:
• a. Diffuse Large B-Cell Lymphoma (DLBCL) not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr Virus (EBV)+ DLBCL of the elderly; OR b. Primary mediastinal (thymic) large B cell lymphoma; OR c. Transformation to DLBCL; OR d. High grade B-cell Lymphoma (HGBL).
• Subjects must not have any signs or symptoms of CNS disease or detectable evidence of CNS disease on magnetic resonance imaging (MRI) at screening; subjects who have been previously treated for CNS disease, but have no evidence of disease at screening are eligible for this cohort.
• Subjects must have disease progression confirmed by either flow cytometry or immunohistochemistry (IHC), disease stabilization, or disease recurrence after at least two lines of therapy.
• a. The two lines of prior therapy must include an anthracycline and anti-CD20 monoclonal antibody treatment.
• b. Relapse or refractory after single antigen targeting CAR T cell therapy
• Must have evaluable or measurable disease according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma; lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
• COHORT 2: MANTLE CELL LYMPHOMA (MCL)
• Mantle Cell Lymphoma (MCL).
• a. Results of all tests conducted on the tissue at initial diagnosis and/or relapse, including, but not limited to, the MCL subtype (classic and blastoid), Ki-67 proliferation index, and TP53 mutation status should be provided if done.
• Subjects must have relapsed and/or refractory MCL confirmed by either flow cytometry or immunohistochemistry (ICH), disease stabilization, or disease recurrence after at least two lines of therapy including any combination of the agents below:
• a. An anti-CD20-directed therapy b. A BTK inhibitor c. Anthracycline or Bendamustine d. Relapse or refractory after single antigen targeting CAR T cell therapy.
• Must have evaluable or measurable disease according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma; lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. MCL patients without measurable nodal or extranodal disease by IWG criteria are eligible if they have bone marrow involvement of MCL at relapse

You may not qualify if:

• Age \< 16 years of age.
• Patient who is intolerant of contrast-enhanced MRI due to allergic reactions to contrast agents. Only applicable to Cohort 3.
• History of other malignancies, unless they have been disease free for at least 3 years. Exceptions include non-melanoma skin cancer or carcinoma in situ and localized prostate cancer not on active treatment.
• Uncontrolled fungal, bacterial, viral, or other infection requiring antimicrobials for management; uncomplicated infections are permitted if responding to active treatment.
• Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (hepatitis B surface antigen \[HBsAg\] positive) or hepatitis C.
• History of known myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment or have cardiac atrial or cardiac ventricular lymphoma involvement.
• Venous thrombosis or embolism not managed on a stable regimen of anticoagulation.
• Any medical condition that in the judgement of the sponsor is likely to interfere with assessment of safety or efficacy of study treatment.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Pregnancy (serum pregnancy test must be obtained at time of enrollment for females of childbearing potential and to be repeated 72 hours prior to lymphodepleting chemotherapy regimen); females who have undergone surgical sterilization or who have been postmenopausal for at least 6 months are not considered to be childbearing potential.
• Lactating.
• In the investigator's judgment, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation.
• Unwilling to participate in long-term follow-up protocol that is required if CAR T cell therapy is administered at CU Anschutz.
• LYMPHODEPLETING CHEMOTHERAPY ELIGIILITY:
• In order to proceed with lymphodepleting chemotherapy, enrolled participants must meet all eligibility criteria below within 72 hours prior to lymphodepletion, unless otherwise specified:

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Recurrence

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Manali Kamdar, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Derek Schatz

CONTACT

7208480628; derek.schatz@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a prospective single-arm Phase 1 with four dose levels. Phase 1 will determine the maximum tolerated dose of CD19x22 CAR T cells using a standard 3+3 trial design in CAR-naïve and CAR-treated patients.

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: October 28, 2021
• Study Start: December 21, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)