CAR-T ceLL for Eradication of Active Residual Disease in LBCL (CLEAR-1 Study)

Rapcabtagene Autoleucel for Eradication of Measurable Residual Disease in Large B-Cell Lymphoma (LBCL)

This is a phase 1b clinical trial to assess the efficacy of rapcabtagene autoleucel (YTB323) administered at the recommended dose in adults with Large B Cell Lymphoma (LBCL) who are at high risk of relapse at end of first line treatment (EOT), as defined by positive measurable residual disease detected by Foresight CLARITY (PhasED-seq). Participants will initially be pre-screened for MRD status after first line treatment (1L) with chemoimmunotherapy including a CD20 monoclonal antibody and anthracycline.

Study Overview

• Status: Not yet recruiting
• Conditions: Large-cell Lymphoma
• Intervention / Treatment: Biological: Rapcabtagene autoleucel (YTB323)

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sunny Salazar; Phone Number: (650) 725-7540; Email: sunnysw@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Eligibility for Pre-Screening:

1. Diagnosis: Histologically confirmed aggressive B cell NHL including the following types defined by WHO 2022[1]:

   • Diffuse large B cell lymphoma (DLBCL); OR

   • Primary mediastinal (thymic) large B cell lymphoma; OR

   • Transformation of indolent lymphomas (eg follicular lymphoma or marginal zone lymphoma)to DLBCL; OR

   • High grade B-cell Lymphoma (NOS, or with MYC/BCL2 rearrangements);
   • Double hit lymphoma (DHL) / Triple hit lymphoma (THL); OR
   • Follicular lymphoma grade 3b
2. Must have 10 unstained slides or tissue block from lymph node excision or core needle biopsy, or a lymph node biopsy (NOT FNA, bone or bone marrow biopsy), in 5 µm thickness FFPE with H&E slide available for ctDNA calibration.
3. Must have intention to complete frontline chemoimmunotherapy including a CD20 monoclonal antibody and anthracycline.
4. In the investigator's assessment, is likely to be eligible to proceed to the treatment portion of this study with intention to undergo YTB323 if MRD positive.
5. Must be able to understand and the willingness to sign the written IRB approved pre-screening informed consent document.

Eligibility Criteria for Screening

1. Diagnosis: Histologically confirmed aggressive B cell NHL including the following types defined by WHO 2022[1]:

• Diffuse large B cell lymphoma (DLBCL); OR
• Primary mediastinal (thymic) large B cell lymphoma; OR
• Transformation of indolent lymphomas to DLBCL; OR
• High grade B-cell Lymphoma;
• Double hit lymphoma (DHL) / Triple hit lymphoma (THL); OR

• Follicular lymphoma grade 3b

  2. Must have completed planned frontline chemoimmunotherapy including a CD20 monoclonal antibody and anthracycline based therapy for LBCL indication with a CR or PR inaccessible for biopsy at end of treatment (EOT 1L).

  3. Circulating tumor DNA is detectable by PhasED-seq within 12 weeks after completion of standard chemoimmunotherapy.

  6. Normal Organ and Marrow Function

  - ANC ≥ 1,000/uL

  • Platelet count ≥ 75,000/uL

  • Adequate renal, hepatic, pulmonary and cardiac function defined as:

    • Creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 45 mL/min
    • Serum ALT or AST ≤ 5 x ULN (except in subjects with liver involvement by lymphoma)
    • Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome.
    • Cardiac ejection fraction ≥ 40%, no evidence of pericardial effusion as determined by an Echocardiogram.
  • No clinically significant pleural effusion or ascites

  • Baseline oxygen saturation > 92% on room air 7. Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential) 8. Contraception: Subjects of child bearing or child fathering potential must be willing to practice birth control from the time of enrollment on this study and for twelve (12) months after receiving the preparative lymphodepletion regimen.

    9. Must be able to understand and the willingness to sign the written IRB approved informed consent document. Subjects unable to give informed consent will not be eligible for this study.

    4. Age 18 years or older 5. Eastern cooperative oncology group (ECOG) performance status of 0, 1, or 2.

Exclusion Criteria:

- 1. Prior treatment with CAR-T or adoptive cell therapy 2. Prior allogeneic transplant. 3. No bridging therapy permitted. 4. Active central nervous system disease from lymphoma. MRI of the brain with no evidence of CNS lymphoma if prior history of CNS involvement.

5. Prior history of allergic reactions to any of the reagents used in the rapcabtagene autoleucel infusion.

6. History of Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, or lymphoplasmacytic lymphoma.

7. History of T-cell histiocyte-rich large B-cell lymphoma. 8. Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment.

9. Women who are pregnant or breastfeeding 10. History of invasive malignancy unless the patient has been disease-free for two years.

Exceptions include nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, and breast) and low grade prostate cancer (e.g. Gleason 3+3) Hormonal therapy in subjects in remission >1 year will be allowed. 11. History of stroke or transient ischemic attack within 12 months before enrollment, or seizure disorders requiring active anticonvulsive medication.

12. In the investigator's judgment, the subject is unlikely to complete all study-specific visits or procedures, including follow-up visits, or comply with the study requirements for participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observational Cohort (MRD-Negative); Participants who are minimal residual disease (MRD) negative following frontline therapy will not receive study intervention and will be followed for subsequent treatments, response, disease status, and survival.
Experimental: Rapcabtagene Autoleucel (YTB323) Treatment Cohort; Participants who are MRD-positive following frontline therapy and meet eligibility criteria will undergo leukapheresis, lymphodepleting chemotherapy, and infusion of rapcabtagene autoleucel (YTB323). Participants will be followed for MRD conversion, safety, disease status, survival, and long-term gene therapy follow-up.	Biological: Rapcabtagene autoleucel (YTB323); Autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy manufactured from participant-derived T cells. Participants undergo leukapheresis for cell collection, receive lymphodepleting chemotherapy, followed by a single intravenous infusion of rapcabtagene autoleucel (YTB323).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimal Residual Disease (MRD) Conversion Rate at Day 90	Proportion of participants who achieve conversion from MRD-positive status at baseline to MRD-negative status at Day 90 (± 2 weeks) following infusion of rapcabtagene autoleucel (YTB323).	Day 90 (3 months ± 2 weeks) post-infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression free survival (PFS) at 12 months from study treatment infusion as compared to historic controls (approximately 18 months from start of frontline therapy).	12 months
Incidence of Adverse Events	Number of participants experiencing treatment-emergent adverse events following infusion of rapcabtagene autoleucel (YTB323), graded according to CTCAE criteria.	From infusion through Day 28 post-infusion
Incidence of Dose-Limiting Toxicities (DLTs)	Number of participants experiencing dose-limiting toxicities (DLTs) following infusion of rapcabtagene autoleucel (YTB323), as defined per protocol.	From infusion through Day 28 post-infusion

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Novartis
• Investigators: Principal Investigator: Saurabh Dahiya, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: February 24, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): March 2, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Lymphatic Diseases; Histiocytic Disorders, Malignant; Histiocytosis; Hemic and Lymphatic Diseases; Dendritic Cell Sarcoma, Interdigitating
• Other Study ID Numbers: IRB-78752; NCI-2026-03512 (Registry Identifier: National Cancer Institute: Clinical Trials Reporting Program)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No