Safety, Efficacy and Pharmacokinetics of XKDCT023 in DLBCL

NCT05269914 | Unknown DMC

• 1 other identifier: XKDCT023-DLBCL
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a phase I multicenter, single arm, open, dose increasing, single treatment clinical study. This study plans to recruit a total of about 10-16 adult patients with CD19 positive recurrent or refractory DLBCL for a single autologous car-t cell therapy. There are three dose groups in the study. The first dose group has one patient. If there is no dose limiting toxicity (DLT), it can be increased to the second dose group, otherwise it will continue to be enrolled according to the "3 + 3" method; The follow-up dose group is conducted according to the traditional "3 + 3" design, that is, three subjects are first enrolled in a dose group. If there is no dose limiting toxicity (DLT) in the three patients in the dose group, it can be increased to the next higher dose after completing the DLT observation period; If DLT occurs in 1 of the 3 patients in the dose group, it is necessary to continue to enroll 3 patients in the dose group for DLT observation. The highest dose level of DLT in less than or equal to 1 of the last 6 confirmed patients will be defined as MTD. The safety of car-t treatment was evaluated by observing the adverse events after cell therapy; Evaluate the effectiveness of car-t treatment compared with the results or historical data of the patient's own previous standard treatment regimen. Blood and bone marrow were collected before and 12 months after cell infusion, the number and activity of car-t cells were detected, and the pharmacokinetics (PK) of car-t cells was evaluated.

Conditions

Diffuse Large B Cell Lymphoma

Keywords

Diffuse large B-cell lymphoma; Autologous anti-CD19 CAR-T cells

Outcome Measures

Primary Outcomes (3)

• Adverse event

  Type, incidence and severity of adverse events

  The follow-up visit within 2 months is allowed to have a time window of ± 2 days, and the follow-up visit from the 3rd to 12th months is allowed to have a time window of ± 5 days.

• Maximum tolerated dose

  The maximum dose that does not cause death of the subject

  The follow-up visit within 2 months is allowed to have a time window of ± 2 days, and the follow-up visit from the 3rd to 12th months is allowed to have a time window of ± 5 days.

• Recommended dose for phase II

  Determine the recommended dose for phase II clinical trials

  The follow-up visit within 2 months is allowed to have a time window of ± 2 days, and the follow-up visit from the 3rd to 12th months is allowed to have a time window of ± 5 days.

Secondary Outcomes (9)

• Peak time,Tmax

  The follow-up visit within 2 months is allowed to have a time window of ± 2 days, and the follow-up visit from the 3rd to 12th months is allowed to have a time window of ± 5 days.

• Maximum concentration, Cmax

  The follow-up visit within 2 months is allowed to have a time window of ± 2 days, and the follow-up visit from the 3rd to 12th months is allowed to have a time window of ± 5 days.

• Area Under Curve, AUC1-30d

  The follow-up visit within 2 months is allowed to have a time window of ± 2 days, and the follow-up visit from the 3rd to 12th months is allowed to have a time window of ± 5 days.

• Pharmacodynamics

  The follow-up visit within 2 months is allowed to have a time window of ± 2 days, and the follow-up visit from the 3rd to 12th months is allowed to have a time window of ± 5 days.

• Total remission rate

  The follow-up visit within 2 months is allowed to have a time window of ± 2 days, and the follow-up visit from the 3rd to 12th months is allowed to have a time window of ± 5 days.

Study Arms (1)

Autologous anti-CD19 CAR-T cell injection

EXPERIMENTAL

with 1.00×106 CAR+T cells/kg, 3.00×106 CAR+T cells /kg and 9.00×106 CAR+T cells/kg

Other: Autologous anti-CD19 CAR-T cell injection

Interventions

Autologous anti-CD19 CAR-T cell injection OTHER

According to preclinical research, existing preliminary clinical data and similar approved therapeutic products (kte-c19 of Kate company, the trade name is yescarta ®） According to the clinical trial results, three doses (the number of cells per unit body weight) were selected as the therapeutic dose of this study. Among the patients who increased the dose according to the "3 + 3" design, the number of target cells in each dose group was: (1) the first dose group was 1.00 × 106 Car + T cells / kg, 20% dose error is allowed. (2) the second dose group is 3.00 × 106 Car + T cells / kg, 20% dose error is allowed. (3) the third dose group is 9.00 × 106 Car + T cells / kg, 20% dose error is allowed.

Autologous anti-CD19 CAR-T cell injection

Eligibility Criteria

• Age: 18 Days - 75 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All subjects or legal guardians must sign the informed consent approved by the ethics committee in writing before starting any screening procedure.
• Adult patients aged 18 and over with recurrent or refractory DLBCL.
• Bone marrow negative or bone marrow lymphoma cells in screening stage determined by CT scan \< 30%.
• The subject had been adequately treated before.
• According to the revised IWG malignant lymphatic efficacy evaluation criteria (2007 Edition), there was at least one measurable lesion in the baseline period.
• Estimated survival ≥ 12 weeks.
• The baseline ECoG score was 0 or 1.
• Adequate organ function.
• Hemodynamics determined by echocardiography or multichannel radionuclide angiography (MUGA) were stable and left ventricular ejection fraction (LVEF) ≥ 45%.
• Sufficient bone marrow reserve without blood transfusion.
• There must be non mobilized apheresis or peripheral blood collected cells for car-t cell production.
• According to the judgment of the researcher, the patient has fully recovered from the toxicity of previous anti-tumor treatment and is suitable for pretreatment chemotherapy and car-t cell treatment.
• Women of childbearing age and all male subjects must agree to use efficient contraceptive methods until at least 12 months after xkdct023 infusion, and until two consecutive PCR tests show that car-t cells are no longer present in the body.

You may not qualify if:

• Patients who have previously received any anti-CD19 / anti-CD3 treatment, or any other anti-CD19 treatment;
• Patients previously treated with any gene therapy product, including car-t treatment;
• Patients with detectable cerebrospinal fluid malignant cells or brain metastasis, or patients with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma;
• Patients with testicular invasion, including patients with orchiectomy;
• Patients with current or history of central nervous system diseases, such as epilepsy, cerebrovascular ischemia / hemorrhage, dementia, cerebellar diseases or any autoimmune diseases involving the central nervous system;
• Patients who had previously received allogeneic hematopoietic stem cell transplantation (HSCT);
• Patients who are suitable and willing to receive autologous hematopoietic stem cell transplantation (ASCT);
• The feasibility evaluation screening stage showed that the lymphocyte transfection efficiency of patients was less than 5%, or patients whose T cell culture could not be expanded (\< 5 times).
• Patients who received chemotherapy other than lymphocyte clearance chemotherapy within 2 weeks before xkdct023 infusion;
• Patients who had received other study drugs within 30 days before screening;
• Patients who received radiotherapy within 2 weeks before infusion;
• Active hepatitis B (defined as hepatitis B virus DNA detection value \> 1000 copies/ml) or hepatitis C virus (HCV RNA positive) patients.
• HIV positive or Treponema pallidum positive patients;
• Patients with acute life-threatening bacterial, viral or fungal infections that have not been controlled (e.g. positive blood culture ≤ 72 hours before infusion);
• Patients with unstable angina pectoris and / or myocardial infarction within 6 months before screening;

Sponsors & Collaborators

• The Affiliated Hospital of Qingdao University: lead

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 Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single infusion of autologous anti-CD19 car-t cells

Study Record Dates

• First Submitted: December 3, 2021
• First Posted: March 8, 2022
• Study Start: April 1, 2022
• Primary Completion: December 31, 2022
• Study Completion: June 30, 2023
• Last Updated: March 8, 2022

Record last verified: 2022-03