Metabolically Fit CD19 CAR T-cell Therapy With CD34 Selection in Patients With CD19+ Relapsed/Refractory NHL, CLL/SLL

NCT05702853 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 103351
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, nonrandomized, open-label dose-escalation study followed by dose-expansion of CD19- CD34t metabolically programmed CAR T-cell therapy in adult patients with relapsed or refractory CD19 B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Conditions

Chronic Lymphocytic Leukemia; B-cell Non Hodgkin Lymphoma

Keywords

NHL; CLL; SLL; CD19; CAR-T; CD34

Outcome Measures

Primary Outcomes (3)

• MTD/MAD/RP2D evaluation

  Maximum tolerated dose (MTD), maximum administered dose (MAD) and the recommended phase 2 dose (RP2D) of CD19-CD34t metabolically programmed CAR T-cells

  12 months

• CRS occurrence evaluation

  Rate of grade 3 or higher cytokine release syndrome(CRS)

  Duration of study, up to 24 months

• ICANS occurrence evaluation

  rate of grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS)

  Duration of study, up to 24 months

Secondary Outcomes (5)

• Overall response and complete remission rate

  12 months

• Progression free survival, duration of response, overall survival evaluations

  12 months

• ORR and CR evaluation at the RP2D

  Duration of study, up to 24 months

• PFS, DOR and OS evaluation at the RP2D

  Duration of study, up to 24 months

• Safety evaluation at the RP2D

  Duration of study, up to 24 months

Study Arms (3)

Dose Level 1

EXPERIMENTAL

1 x 10\^6 transduced T cells/kg (± 20%)

Drug: Cyclophosphamide injection; Drug: Fludarabine Injection; Biological: CD19-CD34t metabolically programmed CAR transduced T-cells

Dose Level 2

EXPERIMENTAL

1.5 x 10\^6 transduced T cells/kg (± 20%)

Drug: Cyclophosphamide injection; Drug: Fludarabine Injection; Biological: CD19-CD34t metabolically programmed CAR transduced T-cells

Dose Level 3

EXPERIMENTAL

2 x 10\^6 transduced T cells/kg (± 20%)

Drug: Cyclophosphamide injection; Drug: Fludarabine Injection; Biological: CD19-CD34t metabolically programmed CAR transduced T-cells

Interventions

CD19-CD34t metabolically programmed CAR transduced T-cells BIOLOGICAL

Cells are to be infused intravenously (IV) over 30 minutes or less via nonfiltered tubing either by gravity or a peristaltic pump, gently agitating the bag during infusion to prevent cell clumping

Dose Level 1; Dose Level 2; Dose Level 3

Fludarabine Injection DRUG

30 mg/m2 IV over 30-60 minutes +/- 10 minutes after cyclo- phosphamide infusion Days -5, 4, -3

Dose Level 1; Dose Level 2; Dose Level 3

Cyclophosphamide injection DRUG

500 mg/m2 IV over 30-60 minutes +/- 10 minutes before Fludarabine Days -5, -4, - 3

Dose Level 1; Dose Level 2; Dose Level 3

Eligibility Criteria

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

You may qualify if:

• Patients eligible for study participation must meet all of the following criteria:
• Disease Related Criteria
• Participants must have histologic confirmation of one of the following:
• CD19+ aggressive non-Hodgkin lymphoma including any of the following subtypes
• Diffuse Large B-cell Lymphoma, not otherwise specified
• DLBCL, germinal-center B-cell type (GCB)
• DLBCL, activated B-cell type (ABC)
• T-cell histiocyte-rich B-cell lymphomas (THRBCL)
• Primary cutaneous DLBCL, leg type
• Intravascular large B cell lymphoma
• EBV+ DLBCL, NOS
• DLBCL associated with chronic inflammation
• HHV8+ DLBCL, NOS
• High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement(double hit lymphoma)
• High grade B-cell lymphoma, NOS

You may not qualify if:

• Participants eligible for study participation CANNOT meet any of the following criteria:
• Prior/Concurrent Therapy Related Criteria Guidelines regarding when lymphoma directed therapy should be stopped prior to leukapheresis, lymphodepleting chemotherapy, and CAR T-cell infusion are detailed in the protocol. These criteria must be planned to be met for all patients.
• Clinical/Laboratory Criteria
• Women who are pregnant or breast-feeding.
• Participants with active CNS lymphoma. Participants can have a history of active CNS lymphoma as outline in protocol
• Participants with evidence of Graft vs Host Disease from allogeneic stem cell transplant are ineligible unless it is either grade 1 involvement of the skin or not requiring systemic immunosuppression.
• Participants with uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment)
• Participants with a history of stroke or intracranial hemorrhage within 6 months prior to registration. Any CNS disorder that would serve as a major barrier in evaluating neurotoxicity/ICANS per enrolling physician
• Participants with prior history of malignancy other than lymphoma unless subject is free of disease for more than 1 year from signing consent. Exceptions include the following:
• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix or breast
• Previously treated localized prostate cancer with normal PSA levels
• Participants with primary immunodeficiency or history of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 1 year.
• Participants with receipt of live vaccine within 28 days prior to registration.

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Brian Hess, PHD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

HCC Clinical Trials Office

CONTACT

843-792-9321; hcc-clinical-trials@musc.edu

Study Design

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

Study Record Dates

• First Submitted: December 7, 2022
• First Posted: January 27, 2023
• Study Start: November 6, 2023
• Primary Completion (Estimated): November 6, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)