CD19/CD22 Bispesifikk CAR-T-celleterapi for tilbakevendende/refraktær stor B-celle lymfom
CD19/CD22 bispesifikk CAR-T-celleterapi for tilbakevendende/refrakter stor B-celle lymfom: En prospektiv, enarms-, enkelt-senter, fase 2-studie
CAR-T cell therapy targeting CD19 has been shown to be effective in heavily-pretreated B-cell ALL or NHL, but relapses post-CAR-T are common, and CD19 antigen loss is one of the reasons. Thus, the investigators supposed that CD19/CD22 bispecific CAR-T cell therapy would be more effective and less relapses would occur in B- NHL. In this prospective phase 2 clinical trial, the investigators aim to explore the efficacy and safety of CD19/CD22 bispecific CAR-T cell therapy in relapsed/refractory Large B cell lymphoma.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
Large B cell lymphoma (LBCL) is the most common aggressive subtype of non-Hodgkin lymphoma (NHL) in adults. While approximately 60% of patients can be cured with first-line therapy, a subset of patients experiences relapse or refractory disease (R/R). The prognosis for R/R LBCL patients is poor, with limited efficacy from traditional treatments such as autologous stem cell transplantation (ASCT) and novel targeted agents. Chimeric antigen receptor-T (CAR-T) cell therapy involves genetically engineering T cells to express chimeric antigen receptors (CARs) that target tumor-specific antigens, enabling precise elimination of tumor cells. CD19 is the most commonly targeted antigen in B-cell malignancies, however, antigen escape following CD19 CAR-T therapy can lead to disease relapse in some patients. Studies indicate that CD22 is widely expressed in B-cell malignancies and exhibits incomplete overlap with CD19 expression, suggesting that dual-target CAR-T therapy may more comprehensively eradicate tumor cells. Therefore, dual-target CAR-T therapy, particularly strategies targeting both CD19 and CD22, has emerged as a promising approach to overcome antigen escape and enhance therapeutic outcomes. In this prospective study, the investigators aimed to evaluate the efficacy and safety of CD19/CD22 bispecific CAR-T cell (CAR2219) therapy in patients with R/R LBCL.
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
-
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Beijing Municipality
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Beijing, Beijing Municipality, Kina, 100730
- Beijing Tongren Hospital, Capital Medical University
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Inclusion Criteria:
- 14 years to 85 years, expected survival > 3 months;
- CD19 positive with or without CD22 positive Large B-cell lymphoma;
- relapsed or refractory disease;
- ECOG-PS score=0-2;
- Having at least one measurable lesion;
- Cardiac function: 1-2 levels;
- Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN;
- kidney: Cr≤1.25ULN;
- bone marrow: WBC ≥ 3.0×10e9/L, Hb ≥80 g/L, PLT ≥ 50×10e9/L;
- No serious allergic constitution;
- No other serious diseases that conflicts with the clinical program;
- No other cancer history;
- No serious mental disorder;
- Informed consent is signed by a subject or his lineal relation.
Exclusion Criteria:
- Pregnant or lactating women (female participants of reproductive potential must have a negative serum or urine pregnancy test);
- Uncontrolled active infection, HIV infection, syphilis serology reaction positive;
- Active hepatitis B or hepatitis C infection;
- With severe cardiac, liver, renal insufficiency, diabetes and other diseases;
- Participate in other clinical research in the past 4 weeks;
- Researchers think of that does not fit to participate in the study, or other cases that affect the clinical trial results.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: CD19/CD22 CAR-T group
Patients would receive autologous CAR-T cell therapy targeting both CD19 and CD22. The dosage for CD19/CD22 bispecific CAR-T cells was 2×10e6/kg. |
CD19/CD22-bispecific CAR-T cells were infused at the dosage of 2×10e6/kg |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
best overall response rate (ORR) as of 3 months post-CAR-T cells infusion
Tidsramme: From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion
|
Overall response rate means sum of complete response rate and partial response rate |
From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Best Complete Response rate (CR) as of 3 months post-CAR-T cells infusion
Tidsramme: From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion
|
CR was defined as complete response evaluated using PET-CT scan |
From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion
|
|
Progression free survival (PFS)
Tidsramme: From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion
|
PFS was defined from the date of CAR-T infusion to the date fo confirmed disease progression or death of any reason |
From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion
|
|
overall survival (OS)
Tidsramme: From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion
|
OS was defined from the date of CAR-T infusion to the date fo death |
From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion
|
|
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Tidsramme: From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion
|
measured using CTCAE version 5.0 |
From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Liang Wang, M.D., Beijing Tongren Hospital
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Andre studie-ID-numre
- TRhos-CART-02
- 2025ZD0544300 (Annet stipend/finansieringsnummer: Noncommunicable Chronic Diseases-National Science and Technology Major Project)
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