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

NCT07443137 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: IRB-78752NCI-2026-03512
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Large-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Progression free survival

  12 months

• Incidence of Adverse Events

  From infusion through Day 28 post-infusion

• Incidence of Dose-Limiting Toxicities (DLTs)

  From infusion through Day 28 post-infusion

Study Arms (2)

Observational Cohort (MRD-Negative)

NO INTERVENTION

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.

Rapcabtagene Autoleucel (YTB323) Treatment Cohort

EXPERIMENTAL

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)

Interventions

Rapcabtagene autoleucel (YTB323) BIOLOGICAL

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).

Rapcabtagene Autoleucel (YTB323) Treatment Cohort

Eligibility Criteria

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

You may qualify if:

• Eligibility for Pre-Screening:
• 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
• 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.
• Must have intention to complete frontline chemoimmunotherapy including a CD20 monoclonal antibody and anthracycline.
• 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.
• Must be able to understand and the willingness to sign the written IRB approved pre-screening informed consent document.
• Eligibility Criteria for Screening
• \. Diagnosis: Histologically confirmed aggressive B cell NHL including the following types defined by WHO 2022\[1\]:
• Diffuse large B cell lymphoma (DLBCL); OR

You may not qualify if:

• \- 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.
• \. Prior history of allergic reactions to any of the reagents used in the rapcabtagene autoleucel infusion.
• \. History of Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, or lymphoplasmacytic lymphoma.
• \. 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.
• \. 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.
• \. 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.

Sponsors & Collaborators

• Novartis: collaborator
• Stanford University: lead

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Saurabh Dahiya, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sunny Salazar

CONTACT

(650) 725-7540; sunnysw@stanford.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: February 24, 2026
• First Posted: March 2, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: June 4, 2026

Record last verified: 2026-06