RGL-305 cell reinfusion for lymphoma patients with positive minimal residual disease after response to standard therapy.

An Exploratory Clinical Study to Evaluate the Safety and Cytodynamic Characteristics of RGL-305 in Patients With Lymphoma

This trial will test whether RGL-305 cell reinfusion is safe and can reduce minimal residual disease in adults with lymphoma who achieved a complete or partial response but remain MRD-positive after standard treatment.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (other)
• Drugs / interventions: CAR-T, chimeric antigen receptor
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07006012 on ClinicalTrials.gov

What this trial studies

This open-label, prospective, dose-escalation trial uses a 3+3 design to test RGL-305 cell reinfusion in lymphoma patients who are MRD-positive after achieving CR or PR with standard therapy. Two preset dose levels (low and high) will each enroll 3–6 patients, with the first subject in each group acting as a sentinel observed for at least 48 hours. The dose-limiting toxicity period is 21 days after the first infusion, and patients may receive up to five infusions given every two weeks (Q2W) unless recurrence, progression, unacceptable toxicity, new anti-tumor therapy, or death occurs. Primary focus is safety and cytodynamic profiling with exploratory signals of initial efficacy measured by MRD and clinical status.

Who should consider this trial

Good fit: Adults 18–75 years old with pathologically confirmed lymphoma who achieved CR or PR after at least one standard treatment, are MRD-positive (PR patients must have Deauville score 4), have ECOG 0–1, and meet required organ-function criteria are ideal candidates.

Not a fit: Patients without detectable MRD, with active progressive disease, poor organ function, ECOG >1, or other contraindications to cell therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, RGL-305 could help eliminate MRD and reduce the risk of relapse in patients who have already responded to standard lymphoma treatments.

How similar studies have performed: Other cellular therapies such as CAR-T have produced durable remissions in some lymphomas, but RGL-305 is a novel investigational product with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily participate in the study and sign a written informed consent
2. Age 18-75 years old (including the boundary value), gender is not limited;
3. Patients with pathologically confirmed lymphoma who have previously received at least one standard treatment. After the last treatment, patients with Lugano 2014 lymphoma efficacy evaluation criteria were CR or PR, and MRD was positive. Patients with PR were required to have a Deauville score of 4.
4. Be willing to provide blood or tissue samples required for cytodynamic and biomarker detection before and after treatment;
5. ECOG score is 0 or 1;
6. Expected survival ≥3 months;
7. The function of vital organs meets the following criteria:

   1. Neutrophil absolute value (ANC) ≥1.0×109/L;
   2. Platelet count (PLT) ≥80×109/L;
   3. Hemoglobin (Hb) ≥90g/L;
   4. International standardized ratio (INR\<1.5), activated partial thromboplastin time (APTT) ≤1.5×ULN;
   5. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 times the upper limit of normal (ULN);
   6. Total bilirubin (TBIL) ≤1.5×ULN;
   7. Serum creatinine (Scr) ≤1.5×ULN;
   8. Left ventricular ejection fraction (LVEF) ≥45%;
   9. Electrocardiogram: Fridericia corrected QT interval (QTcF) \<470 ms; The QTc interval must be corrected according to Fridericia's standard with the correction formula QTcF=QT/RR\^0.33.
8. Fertile female subjects must agree to effective contraception and refrain from egg donation for 6 months from the signing of the informed consent until the last administration of the investigational drug, the serum pregnancy test must be negative within 7 days prior to the first administration, and they are not lactating; Male subjects whose partner is a fertile woman must agree to highly effective contraception and refrain from sperm donation from signing the informed consent until 6 months after the final administration of the investigational drug (see Annex 6 for details)

Exclusion Criteria:

1. Previous adoptive cell therapy, including but not limited to tumor-infiltrating lymphocytes (TILs), chimeric antigen receptor T cells (CAR-T), and T cell receptor chimeric T cells (TCR-T);
2. Have previously received or planned to undergo organ transplantation or allogeneic stem cell or allogeneic bone marrow transplantation;
3. Combined with congenital or acquired immunodeficiency such as cellular immunodeficiency (e.g., DiGeorge syndrome, T-negative severe combined immunodeficiency \[SSCID\]) or combined T-cell and B-cell immunodeficiency (e.g., T-and B-negative combined immunodeficiency, Wiskott-Aldrich syndrome, ataxic telangiectasia, often) See variable immune deficiency); Or infected with human immunodeficiency virus (HIV);
4. The presence of autoimmune diseases, except for patients with hypothyroidism due to autoimmune thyroiditis who only need hormone replacement therapy;
5. History of epilepsy or other central nervous system diseases, or lymphoma invading the central nervous system;
6. Complicated with other malignant tumors, except malignant tumors with disease-free survival of more than 3 years and carcinoma in situ;
7. History of allergy to blood products, known to be allergic to test substances;
8. Any non-hematological toxicity associated with previous treatment does not return to ≤ grade 1, except for hair loss and peripheral neurotoxicity;
9. Those who had undergone major surgery (≥ Grade 3 surgery) within 4 weeks before the start of study treatment, or who required elective surgery during the trial period;
10. Have an poorly controlled or severe cardiovascular disease, such as symptomatic congestive heart failure (NYHA class III or IV), a myocardial infarction within 6 months prior to study initiation, or unstable angina within 1 month prior to study initiation, or an arrhythmia requiring treatment or intervention, Or hypertension remains poorly controlled after adequate treatment (systolic blood pressure ≥150mmHg, diastolic blood pressure ≥90mmHg);
11. Known hereditary or acquired bleeding or thrombotic tendencies;
12. Subjects with a known or highly suspected history of interstitial pneumonia, or evidence of active interstitial pneumonia on chest CT during the pre-screening period; Known history of idiopathic pulmonary fibrosis, institutional pneumonia (such as bronchiolitis obliterans or cryptogenic institutional pneumonia); Subjects who may interfere with the detection or management of suspected drug-related pulmonary toxicity;
13. A severe infection occurring within 28 days prior to study initiation (such as intravenous antibiotics, antifungal, or antiviral drugs as required by clinical practice), or an active infection receiving therapeutic intravenous or oral antibiotics within 14 days prior to study initiation, or an unexplained fever;
14. Active hepatitis B (HBV), hepatitis C (HCV), cytomegalovirus (CMV), EB virus (EBV), HIV, syphilis infection;
15. Plan to receive live attenuated vaccine (inactivated vaccine is allowed) within 28 days before the start of study treatment or during the study period and 90 days after the end of study drug treatment;
16. In the investigator's judgment, the subject has other factors that may affect the study results or lead to the forced termination of the study treatment;
17. During the study period, subjects considering fertility, female subjects became pregnant or breastfed within 6 months of the last study drug administration.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Rong Tao, M.D — Fudan University
• Study coordinator: Rong Tao, M.D

Conditions: Lymphoma Patients With Complete Response or Partial Response After Standard Treatment Had a Positive Minimal Residual Lesion, Lymphoma, DLBCL