CD45BE-HSPC + CART-45 Cells

NCT07451054 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 50425
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, open-label, dose-finding study to assess the safety, feasibility, pharmacokinetics and preliminary efficacy of autologous base edited anti-CD45 CAR T cells (referred to as "CART-45 cells") following an autologous transplant of CD45 base edited hematopoietic stem and progenitor cells (referred to as "CD45BE-HSPC") in patients with relapsed or refractory hematologic malignancies.

Conditions

B-Cell Non-Hodgkin Lymphoma (NHL); Richter's Transformation; T-Cell Non-Hodgkin Lymphoma; Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (4)

• Incidence of Adverse Events as assessed by CTCAE v6.0

  Type, frequency and severity of adverse events as assessed by CTCAE V6.0. Each disease-specific cohort will be analyzed separately.

  Up to 15 years post infusion

• Occurrence of dose-limiting toxicities (DLTs)

  Unacceptable toxicity as defined by the protocol. DLTs will be evaluated separately by each disease-specific cohort.

  28 days post-CART-45 infusion

• Identification of the maximum tolerated dose (MTD)

  Selected based on an isotonic regression model. The MTD will be established separately by disease-specific cohort

  28 days post-CART-45 infusion

• Identification of a recommended dose for expansion (RDE)

  Evaluated by Cohort/dose level using a multi-criteria decision analysis.

  3 months post-CART-45 infusion

Secondary Outcomes (11)

• Proportion of CD45BE-HSPC products that fail to meet the product release criteria

  3 months

• Proportion of CART-45 products that fail to meet the product release criteria

  3 months

• Proportion of CD45BE-HSPC products that fail to meet the protocol-defined dose

  3 months

• Proportion of CART-45 products that fail to meet the assigned dose.

  3 months

• Evaluate study feasibility

  3 months

Study Arms (2)

Cohort A: B-cell Non-Hodgkin Lymphoma (B-cell NHL), Richter's Transformation (RT)

EXPERIMENTAL

Biological: CART-45 cells; Biological: CD45BE-HSPC

Cohort B: T-cell Non-Hodgkin Lymphoma (T-cell NHL), Hodgkin Lymphoma (HL)

EXPERIMENTAL

Biological: CART-45 cells; Biological: CD45BE-HSPC

Interventions

CD45BE-HSPC BIOLOGICAL

CD45 base edited hematopoietic stem and progenitor cells

Cohort A: B-cell Non-Hodgkin Lymphoma (B-cell NHL), Richter's Transformation (RT); Cohort B: T-cell Non-Hodgkin Lymphoma (T-cell NHL), Hodgkin Lymphoma (HL)

CART-45 cells BIOLOGICAL

Autologous base edited anti-CD45 CAR T cells

Cohort A: B-cell Non-Hodgkin Lymphoma (B-cell NHL), Richter's Transformation (RT); Cohort B: T-cell Non-Hodgkin Lymphoma (T-cell NHL), Hodgkin Lymphoma (HL)

Eligibility Criteria

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

You may qualify if:

• \. Signed informed consent form 2. Male or females age ≥ 18 years 3. Disease-Specific Criteria
• a. B-cell Non-Hodgkin Lymphoma (B-cell NHL)- including the following sub-types:
• i. Patients with any of the following large B-cell lymphoma diagnoses who meet the prior treatment criteria outlined below: Diffuse Large B-cell Lymphoma not otherwise specified (DLBCL NOS); Primary Cutaneous DLBCL; Primary Mediastinal (thymic) Large B-cell Lymphoma; ALK+ Anaplastic Large B-cell Lymphoma; High-Grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 rearrangements (i.e., "Double or Triple Hit"); High-grade B-cell Lymphoma, NOS; T-cell Rich B-cell Lymphoma; Transformed Follicular Lymphoma; or any aggressive B-cell lymphoma arising from indolent lymphoma.
• \. Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND 2. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy.
• ii. Follicular Lymphoma
• Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
• Relapsed/refractory disease after at least 2 prior lines of systemic therapy (not including a single agent monoclonal antibody therapy).
• iii. Mantle Cell Lymphoma
• Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
• Relapsed/refractory disease after at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (TKI) inhibitor. Single-agent monoclonal antibody therapy does not count towards prior lines of therapy.
• iv. Marginal Zone Lymphoma- relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a Bruton tyrosine kinase (TKI) inhibitor. Note: Single-agent monoclonal antibody therapy does not count towards prior lines of therapy.
• b. T-cell Non-Hodgkin Lymphoma (T-cell NHL)
• i. Histologically or cytologically confirmed relapsed or refractory (r/r) mature aggressive T- and NK-cell neoplasms as defined in the 5th edition of the WHO Classification of Hematolymphoid tumors, which includes any of the following diagnoses:
• Peripheral T-cell Lymphoma, NOS (PTCL-NOS);
• Nodal T-cell Lymphomas with T Follicular Helper \[TFH\] Phenotype, including Follicular T cell Lymphoma, Angioimmunoblastic Lymphoma, or Anaplastic Large Cell Lymphoma (ALCL);

You may not qualify if:

• Active hepatitis B or hepatitis C infection
• Any active, uncontrolled infection.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
• Severe, active co-morbidity that, in the opinion of the physician-investigator, would preclude participation in this study.
• Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Active acute or chronic GVHD requiring systemic therapy.
• Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.
• Active CNS involvement. Patients with a history of CNS involvement that was successfully treated are eligible. A CNS evaluation is only required for eligibility if a subject is experiencing signs/symptoms of CNS involvement.
• Patients with evidence of a circulating T-cell malignancy as measured by flow cytometry.
• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
• Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Kite, A Gilead Company: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, T-Cell; Hodgkin Disease

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

Study Officials

• Noelle Frey, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abramson Cancer Center Clinical Trials Service

CONTACT

215-349-8245; PMCancerResearch@Pennmedicine.upenn.edu

Study Design

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

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 5, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2051
• Study Completion (Estimated): July 1, 2051
• Last Updated: June 10, 2026

Record last verified: 2026-06

Locations

US (1)