Phase I Clinical Trial of RC19D2 Cell Injection in the Treatment of Diffuse Large B-cell Lymphoma

NCT06047197 | Recruiting Phase 1

• 1 other identifier: RC19D2-r/r DLBCL-01
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is a phase I clinical trial aimed at the safety and tolerability of RC19D2 cell injection in the treatment of CD19 positive patients with recurrent or refractory diffuse large B-cell lymphoma

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-cell Lymphoma

Keywords

CD19; CAR-T; RC19D2; DLBCL

Outcome Measures

Primary Outcomes (2)

• MTD

  Determine the maximum tolerable dose(MTD) based on the 28 day dose limit toxicity occurrence of all participants.

  28 days

• AE Safety

  Number of participants with Adverse event (AESI, ADR, SAE, etc.), with abnormal laboratory test results, abnormal vital signs, abnormal physical examination findings and abnormal 12 lead electrocardiogram readings

  2 years

Study Arms (4)

First dose group

EXPERIMENTAL

The initial dose is (0.5 ± 0.1) × 10\^6/kg, with 1 participant enrolled

Biological: RC19D2 cell injection

Second dose group

EXPERIMENTAL

The second dose is (1.0 ± 0.2) × 10\^6/kg, with 3-6 study participants enrolled

Biological: RC19D2 cell injection

Third dose group

EXPERIMENTAL

The third dose is (2.5± 0.5) × 10\^6/kg, with 3-6 study participants enrolled

Biological: RC19D2 cell injection

Fourth dose group

EXPERIMENTAL

The fourth dose is (5± 1) × 10\^6/kg, with 3-6 study participants enrolled

Biological: RC19D2 cell injection

Interventions

RC19D2 cell injection BIOLOGICAL

The functional component of RC19D2 cell injection is T cells that have been genetically modified to express anti CD19 chimeric antigen receptors.

First dose group; Fourth dose group; Second dose group; Third dose group

Eligibility Criteria

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

You may qualify if:

• Understand and voluntarily sign the informed consent form;
• Age ≥ 18 years old at the time of screening, regardless of gender;
• Patients with diffuse large B-cell lymphoma who have been diagnosed as CD19 positive by histopathology and/or cytology, but have failed standard treatment in the early stage, and currently lack effective treatment methods for recurrent or refractory CD19 positive.
• The regulations for the past treatment status of research participants are as follows (meeting at least one of them): 1.At least after sufficient second-line treatment (CD20 positive individuals must have already used sufficient amounts of CD20 targeted drugs and anthracycline drugs), recurrence, no remission, or progression; In the first two lines of treatment, if the optimal therapeutic effect is SD, then the line of treatment must have completed 2 cycles;2.Recurrence, unrelieved, or progression after autologous hematopoietic stem cell transplantation;
• According to the 2023 NCCN Lymphoma Treatment Guidelines and the 4th edition of the WHO Lymphatic Tissue Tumor Classification in 2016, the following types were included in this trial:Diffuse large B-cell lymphoma (DLBCL) non-specific (DLBCL-NOS)；Transforming follicular lymphoma (tFL)；High grade B-cell lymphoma (HGBL) with MYC, BCL2, and/or BCL6 rearrangement；High grade B-cell lymphoma, non-specific (HGBL-NOS)；Primary mediastinal large B-cell lymphoma (PMBL)；Grade 3b follicular lymphoma (FL3b);
• Expected survival time ≥ 12 weeks;
• There are measurable target lesions in imaging: the length and diameter of lesions in lymph nodes ≥ 15mm, or extranodal lesions\>10mm (according to Lugano2014 standard); Lesions that have received radiotherapy in the past are considered measurable only when there is clear progress after completing radiotherapy;
• During screening, laboratory inspections must meet the following requirements:Neutrophil count ≥ 1.0 × 10\^9/L;Lymphocyte count ≥ 0.3 × 10\^9/L; Hemoglobin ≥ 70 g/L;Platelets ≥ 50 × 10\^9/L;Total serum bilirubin ≤ 2.0 × Upper limit of normal value (ULN);Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN;Creatinine\<1.5 × ULN and endogenous creatinine clearance rate ≥ 60 mL/min (creatinine clearance rate Cockcroft Fault method: male creatinine clearance rate=\[(140 age) × Weight (kg)\]/\[0.818 × Creatinine（ μ Mol/L)\]; Female creatinine clearance rate=\[(140 age) × Body weight (kg) × 0.85\]/\[0.818 × Creatinine（ μ Mol/L)\].
• The lung function is good, and the blood oxygen saturation of the fingertip pulse under non oxygen inhalation is ≥ 92%;
• The Eastern Oncology Collaborative Group (ECOG) physical fitness score is 0 or 1;
• Head MRI shows no central nervous system lymphoma;
• Cardiac ultrasound shows left ventricular ejection fraction ≥ 50%; No clinically significant abnormal electrocardiogram findings; No clinically significant pericardial or pleural effusion;
• Adequate venous access (for single collection) and no other contraindications for blood cell separation;
• The screening period blood pregnancy test for female participants of childbearing age must be negative

You may not qualify if:

• Individuals with a history of allergies to any component in cellular products;
• Individuals with a history of allogeneic hematopoietic stem cell transplantation;
• Individuals with a history of organ transplantation;
• hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg) are positive; Hepatitis B e antibody (HBe Ab) and/or hepatitis B core antibody (HBc Ab) are positive, and the HBV-DNA quantity is higher than the upper limit of normal value; Hepatitis C virus antibody (HCV Ab) is positive and HCV RNA quantification is higher than the upper limit of normal values; Positive for human immunodeficiency virus antibody (HIV-Ab); Positive anti Treponema pallidum antibody (TP Ab); Cytomegalovirus DNA quantification is higher than the upper limit of normal values; EB virus DNA quantification is higher than the upper limit of normal values;
• CNS diseases that have clinical significance in the past or screening, such as epilepsy, epileptic seizures, paralysis, aphasia, cerebral vascular ischemia/bleeding, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, mental illness, etc;
• Patients with active primary or secondary central nervous system (CNS) lymphoma (patients with CNS disease symptoms must undergo lumbar puncture examination to rule out CNS lymphoma).
• Those who have previously received other genetically modified T cell therapies, or other CAR-T therapies, or any other targeted therapy against CD19;
• Having severe genetic or autoimmune diseases (such as systemic lupus erythematosus);
• Screening for thromboembolic events within the first 6 months (such as myocardial infarction, pulmonary infarction, deep vein thrombosis, and other systemic thrombotic diseases);
• Screening for malignant tumors other than those indicated in this study within the first 5 years, except for tumors in situ (such as cervical cancer, bladder, breast cancer) or non melanoma skin cancer;
• Active or uncontrollable infections that require systemic treatment;
• Within 9 months prior to PBMC collection, received treatment with Bendamustine、Alenzumab, Fludarabine,and Cladribine;;
• Within 4 weeks prior to PBMC collection, patients received naloxamine, calcineurin inhibitors, chemotherapy drugs (methotrexate, cyclophosphamide, ifosfamide, benzoate nitrogen mustard or mefalam,), mycophenolate, thalidomide, immunosuppressive antibodies such as anti TNF, anti IL6, or anti IL6R therapy, tumor radiotherapy, or drugs that can bind to FKBP 12 protein (such as rapamycin, tacrolimus, everolimus, etc.);
• Long acting cell growth factors (such as polyethylene glycol recombinant human granulocyte stimulating factor PEG-rhG-CSF) were used within 3 weeks prior to PBMC collection;
• Received granulocyte macrophage colony stimulating factor (GM-CSF) treatment within 2 weeks prior to PBMC collection;

Sponsors & Collaborators

• Beijing Yongtai Ruike Biotechnology Company Ltd: lead

Study Sites (1)

Hematology Hospital of the Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• lugui Qiu, MD

  blood diseases hospital，chinese academy of medical sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

lugui Qiu, MD

CONTACT

13821266636; qiulg@ihcams.ac.cn

dehui Zou, MD

CONTACT

13602100955; zoudehui@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2023
• First Posted: September 21, 2023
• Study Start: September 5, 2023
• Primary Completion (Estimated): September 5, 2026
• Study Completion (Estimated): December 5, 2026
• Last Updated: August 27, 2024

Record last verified: 2024-08

Locations

CN (1)