A Phase I Clinical Trial of RS001 in Patients with Relapsed/Refractory B-Cell Malignancies

NCT06894693 | Not Yet Recruiting Phase 1

• 1 other identifier: RS001-BCM001
• Study Type: interventional
• Target: 13
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is an open-label, single-arm, dose-escalation and dose-expansion study to evaluate the safety, maximum tolerated dose, pharmacokinetic profile in the body after infusion of RS001 injection, and preliminary efficacy in subjects with CD19-positive relapsed/refractory B-cell malignancies (BCM).

Conditions

B-cell Non-Hodgkin's Lymphoma; Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicity (DLT)

  To evaluate the safety, tolerability, and determine the recommended dosage of RS001 for BCM subjects.

  Up to 28 days

• Maximum Tolerated Dose (MTD)

  MTD is the highest dose for DLT in ≤1/6 subjects.

  Up to 28 days

• Incidence of abnormalities

  Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.

  Up to 28 days

Secondary Outcomes (12)

• Pharmacokinetics (PK) indicator (Cmax)

  Up to 90 days

• Pharmacokinetics (PK) indicator (AUC)

  Up to 90 days

• Pharmacokinetics (PK) indicator (Tmax)

  Up to 90 days

• Pharmacokinetics (PK) indicator (T1/2)

  Up to 90 days

• Overall Response Rate

  Up to 2 years

Study Arms (1)

RS001 injection

EXPERIMENTAL

The trial is divided into two parts: Part A is a dose escalation trial with three dose groups (5×10\^6 CAR+ cells/kg, 1×10\^7 CAR+ cells/kg and 2×10\^7 CAR+ cells/kg at day 0), with 7-18 patients planned to be enrolled. Part B is a dose-expansion trial in which 6\~12 patients will receive RS001 infusions at RP2D dose levels.

Biological: RS001 injection

Interventions

RS001 injection BIOLOGICAL

CD19-CAR-mbIL15-DNT Cells.

RS001 injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily sign an ICF and expect to complete the subsequent follow-up.
• Aged 18 to 75 years (including cut-offs), regardless of gender.
• Meet one of the following B-cell malignancies:
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• B-cell non-Hodgkin's lymphoma diagnosed as CD19-positive by cytology or histopathology according to WHO 2022 criteria, including pathologically confirmed (1) diffuse large B-cell lymphoma, non-specific type (DLBCL, NOS); (2) follicular lymphoma histopathologically graded as grade 3b (FL3b); (3) follicular lymphoma with diffuse large B-cell transformation; (4) primary mediastinal large B-cell lymphoma (PMBCL); (5) high-grade B-cell lymphoma (HGBCL).
• Relapsed/refractory B-cell non-Hodgkin lymphoma, defined as meeting one or more of the following criteria:
• \- Definition of relapse: Relapse after achieving remission (PR and CR) with second-line or higher therapy;
• Definition of refractory: No response to second-line or more therapy: The best efficacy of last therapy is PD or SD (SD requires at least 2 cycles of treatment); Recurrence (must have biopsy-proven recurrence) or progression within 12 months of autologous stem cell transplantation (ASCT) . If salvage therapy, no response to last therapy (SD or PD).
• Subjects must have received adequate treatment in the past, which should include the following treatments:
• Anti-CD20 monoclonal antibody, unless the investigator determines that the tumor is CD20 negative;
• Chemotherapy containing anthracycline drugs;
• For subjects with transformed follicular lymphoma (tFL) who have been previously treated with follicular lymphoma (FL) chemotherapy and with transformation to DLBCL show refractory to chemotherapy.
• ECOG performance status 0 to 1.
• The presence of a measurable lesion that meets one of the following criteria:
• The long axis of the lymph node lesion exceeds 15 mm in length (the short axis is measurable);

You may not qualify if:

• Other malignancies within 5 years prior to screening, except adequately treated carcinoma in situ of the cervix, basal cell or squamous epithelial cell skin cancer, post-radical localized prostate cancer, post-radical ductal carcinoma in situ, and post-radical thyroid cancer;
• Any unstable systemic disease: including but not limited to active infection (other than local infection), unstable angina, cerebrovascular accident or transient ischaemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association class III or IV cardiac insufficiency, refractory hypertension (refractory hypertension is defined as blood pressure that has not reached standard after \>1 month of reasonably tolerable treatment with ≥3 antihypertensive drugs (including diuretics) at adequate doses based on lifestyle improvement or blood pressure that is not effectively controlled with ≥4 antihypertensive drugs), severe cardiac arrhythmias requiring pharmacologic treatment, hepatic arrhythmias, liver diseases, kidney diseases or metabolic disorders;
• Patients with B-cell non-Hodgkin's lymphoma with active central nervous system invasion.
• Patients with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titres not within the normal reference range, positive hepatitis C virus (HCV) antibody and peripheral blood HCV RNA ,positive for human immunodeficiency virus (HIV), or positive for cytomegalovirus (CMV) DNA, or positive syphilis test.
• Subjects who are receiving systemic steroids prior to screening and who are judged by the investigator to require long-term treatment with systemic steroids during the treatment period (except for inhaled or topical use).
• Previous organ transplantation or preparation for organ transplantation (except for haematopoietic stem cell transplantation).
• Persons with acute/chronic Graft-vs-Host Disease (GvHD).
• Patients have received a haematopoietic stem cell transplant within 2 months prior to screening.
• Patients who have previously received any CD19-CAR-T/NK cell therapy, or received CAR-T/NK cell therapy targeting other antigens within the three months prior to screening.
• Active neurological autoimmune or inflammatory diseases (e.g. Guillain-Barre Syndrome (GBS), Amyotrophic lateral sclerosis (ALS)).
• Clinically significant active cerebrovascular diseases (such as cerebral edema, posterior reversible encephalopathy syndrome).
• Patients with a life expectancy of less than 3 months.
• Participants who have previously been involved in other interventional clinical studies and received active investigational drugs, with the last use of an unapproved new drug being less than 28 days prior to signing the informed consent for this trial, or the last use of an approved drug being less than five half-lives prior to cell infusion.
• Received attenuated live vaccine within 6 weeks prior to lymphodepletion.
• The subjects have contraindications or hypersensitivity reactions to fludarabine, cyclophosphamide, tocilizumab, investigational product and its ingredients.

Sponsors & Collaborators

• Guangdong Ruishun Biotech Co., Ltd: lead

MeSH Terms

Conditions

Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Study Officials

• JunYuan Qi, MD, PHD

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

JunYuan Qi, MD, PHD

CONTACT

18622662361; qijy@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2025
• First Posted: March 25, 2025
• Study Start: April 1, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 25, 2025

Record last verified: 2025-03