Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07451054

CD45BE-HSPC + CART-45 Cells

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.

Recruiting

Interested in participating?

Request Info

Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location status: Recruiting

Location contact

Abramson Cancer Center Clinical Trials Service

CONTACT

[email protected]

215-349-8245

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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);
  • ALK+ or ALK-, Enteropathy-Associated T-cell Lymphoma (EATL);
  • Monomorphic Epitheliotropic Intestinal T-cell Lymphoma (MEITL);
  • Extranodal NK/T-cell Lymphoma;
  • Primary Cutaneous T-cell Lymphoma (CTCL);
  • Transformed Mycosis Fungoides (tMF) without blood involvement;
  • Primary Cutaneous Aggressive Epidermotropic CD8+ Cytotoxic T-Cell Lymphoma;
  • Subcutaneous Panniculitis-like T-cell Lymphoma.

ii. Must have received at least one prior line of systemic therapy for their lymphoma. Additional prior treatment provisions required for the following indications:

  • Participants with Anaplastic Large Cell Lymphoma (ALCL) must have received prior Brentuximab vedotin, unless contraindicated.
  • Participants with Subcutaneous Panniculitis-like T-cell Lymphoma or Transformed Mycosis Fungoides (tMF) must have received at least 2 prior lines of systemic therapy.

c. Hodgkin Lymphoma (HL)

i. Patients with histologically proven classical Hodgkin Lymphoma that is CD45 positive by IHC or flow cytometry by a CLIA certified laboratory; AND

ii. Relapsed/refractory disease after at least 2 prior lines of therapy which must include the following:

  • Brentuximab vedotin and immune checkpoint inhibitors (unless contraindicated); AND
  • Autologous stem cell transplant (unless patient has chemorefractory disease to salvage treatment) d. Large Cell Transformation of CLL (Richter's Transformation) i. Patients must be primary refractory or received at least 1 prior line of treatment for Richter's Transformation.
  • Patients are appropriate candidates for autologous HSCT as per physician-investigator clinical discretion
  • Patients with relapsed disease after prior allogeneic SCT must meet the following criteria:

a. Have no active GVHD and require no immunosuppression

b. Are more than 6 months from transplant at the time of physician-investigator confirmation of eligibility

  • Adequate organ function defined as:
  • Serum creatinine ≤ 1.5x ULN or estimated creatinine clearance ≥ 35 mL/min and not on dialysis
  • ALT/AST ≤ 3 x ULN
  • Direct bilirubin ≤ 2.0 mg/dl; for patients with Gilbert's syndrome direct bilirubin must be ≤ 3.0 mg/dl
  • Left Ventricular Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
  • DLCO > 45% predicted value; adjusted for level of hemoglobin
  • Must have minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air 7. ECOG Performance Status 0-1

Exclusion criteria

  • 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.

Treatment and study plan

CART-45 cells

Biological

Autologous base edited anti-CD45 CAR T cells

CD45BE-HSPC

Biological

CD45 base edited hematopoietic stem and progenitor cells

Primary outcomes

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

    Time frame: Up to 15 years post infusion

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

  2. Occurrence of dose-limiting toxicities (DLTs)

    Time frame: 28 days post-CART-45 infusion

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

  3. Identification of the maximum tolerated dose (MTD)

    Time frame: 28 days post-CART-45 infusion

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

  4. Identification of a recommended dose for expansion (RDE)

    Time frame: 3 months post-CART-45 infusion

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

Secondary outcomes

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

    Time frame: 3 months

    Calculated based on the proportion of subjects with CD45BE-HSPC products that fail to meet the product release criteria, out of the number of subjects in whom manufacturing was attempted.

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

    Time frame: 3 months

    Calculated based on the proportion of subjects with CART-45 products that fail to meet the product release criteria, out of the number of subjects in whom manufacturing was attempted.

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

    Time frame: 3 months

    Calculated based on the proportion of subjects with CD45BE-HSPC products that fail to meet the assigned dose, out of the number of subjects in whom manufacturing was attempted.

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

    Time frame: 3 months

    Calculated based on the proportion of subjects with CART-45 products that fail to meet the assigned dose, out of the number of subjects in whom manufacturing was attempted.

  5. Evaluate study feasibility

    Time frame: 3 months

    Proportion of eligible patients who receive both investigational products as planned; by individual disease-specific cohort and in aggregate.

  6. Engraftment of CD45BE-HSPC

    Time frame: 28 days after treatment

    Number of subjects with engraftment of CD45BE-HSPC.

  7. Overall survival (OS)

    Time frame: Up to 15 years after last CART-45 Cells administration

    Duration of time from CD45BE-HSPC infusion (Day 0) to the date of death, for any reason

  8. Overall Response/Remission Rate (ORR)

    Time frame: Up to 12 months following CART-45 administration

    Proportion of subjects with CR or PR at Month 3 as compared to baseline.

  9. Best Overall Response (BOR)

    Time frame: Up to 12 months following CART-45 administration

    Proportion of subjects with a best objective disease response of CR or PR recorded between Month 3 and the end of primary follow-up (Month 12); or start of new anticancer therapy, whichever comes first.

  10. Duration of Response (DOR)

    Time frame: Up to 12 months following CART-45 administration

    Time from the date when the response criteria of CR or PR is first met (at or following Month 3), to the date of confirmed disease progression, death, or other censoring event as described below.

  11. Progression-Free Survival (PFS)

    Time frame: Up to 15 years after product administration

    The duration of time from the CD45BE-HSPC transplant (Day 0) to the date of confirmed disease progression or death, whichever occurs first. Otherwise, PFS will be censored at the date of the last response assessment, date of new anti-cancer treatment is initiated (including CART-45 retreatment) or the data cut-off date; whichever occurs first.

Study contacts

Contact information is provided by the study sponsor or research team.

Abramson Cancer Center Clinical Trials Service

CONTACT

[email protected]

215-349-8245

Sponsors and collaborators

Lead sponsor

University of Pennsylvania

Other

Collaborators

  • Kite, A Gilead Company

Registry information

Official study title

Phase 1 Study of Autologous Anti-CD45 CAR T Cells in Combination With CD45 Base Edited HSPCs in Patients With Relapsed or Refractory Hematologic Malignancies

Important dates

Study start
2026
Primary completion
2051
Study completion
2051
First posted
Mar 5, 2026
Registry last updated
Jun 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.