A Tolerability, Safety and Efficacy Study of RJMty19 in Subjects With Relapsed or Refractory B-NHL

NCT06314828 | Not Yet Recruiting Phase 1

• 1 other identifier: RJMty19-B-NHL002
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 1, open-label, single-arm study to evaluate tolerability, safety and efficacy of RJMty19 in adult subjects with r/r B-NHL.

Conditions

B-cell Non-Hodgkin's Lymphoma

Keywords

off-the-shelf cell product; CAR-DNT; Cell Therapy; B-NHL

Outcome Measures

Primary Outcomes (3)

• Dose-Limiting Toxicity (DLT)

  To evaluate the safety, tolerability, and determine the recommended dosage of RJMty19 for R/R B-NHL 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 (10)

• 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)

RJMty19 (CD19-CAR-DNT Cells)

EXPERIMENTAL

The trial is divided into two parts: Part A is a dose escalation trial with four dose groups (5×10\^6 CAR+ cells/kg, 1×10\^7 CAR+ cells/kg, 2×10\^7 CAR+ cells/kg and 4×10\^7 CAR+ cells/kg at day 0), with 8-24 patients planned to be enrolled. Part B is a dose-expansion trial in which 3\~6 patients will receive RJMty19 infusions at RP2D dose levels.

Biological: RJMty19 (CD19-CAR-DNT cells)

Interventions

RJMty19 (CD19-CAR-DNT cells) BIOLOGICAL

Lentiviral vector-transducted double negative T cells (DNT) to express anti-CD19 CAR. Prior to cellular infusion, each patient received cyclophosphamide, fludarabine and Etoposide lymphodepleting chemotherapy.

RJMty19 (CD19-CAR-DNT Cells)

Eligibility Criteria

• Age: 18 Years - 65 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 65 years (including cut-offs), regardless of gender.
• 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's lymphoma, provided one of the following conditions is met:
• 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.
• 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.
• Subjects have participated in other interventional clinical studies within 3 months prior to screening.
• Received attenuated live vaccine within 6 weeks prior to lymphodepletion.
• The subjects have contraindications or hypersensitivity reactions to fludarabine, cyclophosphamide, etoposide, tocilizumab, investigational product and its ingredients.
• Remaining within the washout period of other antitumor treatments prior to lymphodepletion.

Sponsors & Collaborators

• Guangdong Ruishun Biotech Co., Ltd: lead
• Ruijin Hospital: collaborator
• Southern Medical University, China: collaborator
• Beijing GoBroad Hospital: collaborator

MeSH Terms

Conditions

Lymphoma, B-Cell

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

Central Study Contacts

Weili Zhao, MD,PhD

CONTACT

+862164370045; zhao.weili@yahoo.com

Zixun Yan, MD,PhD

CONTACT

+862164370045; yzx12119@rjh.com.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 11, 2024
• First Posted: March 18, 2024
• Study Start: May 20, 2024
• Primary Completion: May 20, 2025
• Study Completion (Estimated): May 20, 2027
• Last Updated: March 18, 2024

Record last verified: 2024-01