Health TrialsbyHealthPanel

Novel Allogenic CD19-targeting CAR-γδT Cell Therapy (QH103E) in r/r NHL

ConditionNon-hodgkin Lymphoma,B Cell
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorChinese PLA General Hospital

About this trial

CD19-CAR-γδT cell therapy is a cellular immunotherapy targeting CD19 to perform CAR modification on allogeneic γδT cells. A novel version of the CAR-γδT product by gene editing (QH103E) that has been validated for resistance to alloreactive T cell killing and enhancement of memory efficacy will be used in this study.

This is a single center, prospective, open-label, single-arm, phase 1/2 study. A total of around 30 patients with relapsed or refractory (r/r) B-cell non-Hodgkin's lymphoma (NHL) will be enrolled in the study and receive QH103E product infusion. Phase 1 (n=9 to 12) is dose escalation part, and phase 2 (n=15 to 20) is expansion cohort part. The primary objective of this study was to evaluate the safety and efficacy of QH103E in patients with r/r B-cell NHL.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 18-75 (inclusive).

Patients with histologically confirmed CD19-positive B-cell NHL.

PD as best response to first-line therapy, or

SD as best response after at least 4 cycles of first-line therapy (eg,4 cycles of R-CHOP), or

Disqualifiers

No obvious hereditary diseases.

Able to understand the requirements and matters of the trial, and willing to participate in clinical research as required.

Informed consent must be signed.

During the screening period, there was central nervous system (CNS) invasion or a history of clinically significant central nervous system diseases, such as epilepsy and cerebrovascular diseases.

Trial design

Design model

Single group

Treatments tested in this trial

  • Allogenic CD19-CAR-γδT cell

    Biological/Vaccine

    Phase 1 dose escalation (3+3) : dose 1 (1 × 10\^6 cells/kg) , dose 2 (3 × 10\^6 cells/kg), dose 3 (6× 10\^6 cells/kg); Phase 2 : dose of RP2D.

  • Fludarabine

    Drug

    Intravenous fludarabine 30\~50 mg/m\^2/day on days -5, -4, and -3.

  • Cyclophosphamide

    Drug

    Intravenous cyclophosphamide 500\~1000 mg/m\^2/ day on days -5, -4, and -3.

Treatment groups

30 Participants
are divided into 1 treatment group
Group A: Patients with refractory or relapsed B-cell NHLExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Phase 1: Incidence of Adverse Events (AEs)

AE is defined as any adverse medical event from the date of lymphodepletion to 12 months after QH103E infusion. Among them, cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria, graft-versus-host disease (GVHD) according to criteria defined by the Mount Sinai Acute GVHD International Consortium. Other AEs were graded according to common terminology criteria for adverse events (CTCAE) v5.0.

Time frame
12 months
2

Phase 1: Incidence of Dose-Limiting Toxicities (DLTs)

DLT was defined as QH103E-related events with onset within first 28 days following infusion: * Grade 3 aGVHD that does not resolve to Grade 1 or 2 within 7 days, with the exception of isolated skin involvement aGVHD; * Grade 4 CRS, or grade 3 CRS that does not resolve to grade 2 or lower within 2 weeks; * Grade 3 ICANS lasting for ≥7 days or Grade 4 ICANS; * Any other Grade ≥4 and Grade 3 AE related to the QH103E that lasts for ≥14 days, except hematology toxicity.

Time frame
28 days
3

Phase 1: Recommended phase 2 dose (RP2D)

The recommended dose for phase 2 was determined through phase 1 study

Time frame
12 months
4

Phase 2: Best objective Response Rate

The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as the best response to treatment assessed by investigators and based on the Lugano 2014 assessment criterion.

Time frame
12 months

Secondary outcomes

1

Phase 2: Overall Survival (OS)

OS is defined as the time from QH103E infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.

Time frame
12 months after the first infusion of QH103E infusion
2

Phase 2: Progression Free Survival (PFS)

PFS is defined as the time from the QH103E infusion date to the date of disease progression assessed by investigators and based on the Lugano 2014 assessment criterion, or death any cause. Participants not meeting thecriteria for progression by the analysis data cutoff date were censored at their last evaluable disease assessment date.

Time frame
12 months after the first infusion of QH103E infusion
3

Phase 2: Duration of Response (DOR)

DOR is defined as the date of their first CR or PR (which is subsequently confirmed) to PD assessed by investigators and based on the Lugano 2014 assessment criterion for r/r B-cell NHL, or death regardless of cause.

Time frame
12 months after the first infusion of QH103E infusion
4

Pharmacokinetics: Number and copy number of QH103E (phase 1 and phase 2)

Number and copy number of QH103E were assessed by number in peripheral blood. Blood samples were collected before and one year after cell infusion (QH103E were not detected for two consecutivetimes) to detect the number and copy number of QH103E, and to evaluate the pharmacokinetics of QH103E.

Time frame
12 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Chinese PLA General Hospital

Lead sponsor

Source ClinicalTrials.gov
Apply now