Anti-CD19 Chimeric Antigen Receptor Modified T-cell (CAR-T) Therapy for Treatment of B-cell Hematological Malignancies
A Single Arm, Open-labelled Phase II Clinical Trial of Anti-CD19 Chimeric Antigen Receptor Modified T-cell (CAR-T) for Treatment of B-cell Haematological Malignancies
Chi Kong Li
20 participants
Jun 1, 2024
INTERVENTIONAL
Conditions
Summary
CAR-T therapy is now available as a commercial product for treatment of relapsed /refractory acute lymphoblastic leukaemia and B-lymphoma. There is limited access to this new treatment as the product is very expensive. It is imperative to develop cost effective, closed circuit manufacturing systems for CAR-T cells to make CAR-T cells a point-of care production option. Hong Kong Institute of Biotechnology has established a certified GMP facility and utilize the Prodigy system to manufacture CAR-T cells for clinical application. Prince of Wales Hospital and Hong Kong Children's Hospital will conduct the phase II clinical trial to confirm the efficacy and safety of local manufactured CAR-T cell product.
Eligibility
Inclusion Criteria14
- Acute Lymphoblastic Leukaemia
- Paediatric or adult patients with relapsed or refractory CD19+ B cell ALL. (Age 0-60 years). Patients should be in first or subsequent relapse, or relapse after prior stem cell transplant, or persistent Minimal Residual Disease (MRD) positive disease
- ECOG performance score of ≤2 if \>16 years old, or Lansky performance score of \>50 if ≤16 years old at screening
- Post allogeneic stem cell transplant patients with B cell ALL will be eligible \> 3 months after transplant and off immunosuppression for at least 1 month.
- Patients with active leukaemia who developed significant organ impairment that cannot tolerate conventional chemotherapy,
- For women of childbearing potential, a negative pregnancy test prior to apheresis
- B-cell lymphoma
- Patients with histologically confirmed refractory Diffuse Large B-cell Lymphoma, primary mediastinal B cell lymphoma or transformed follicular lymphoma or other B-cell lymphoma according to WHO classification
- Confirmed CD19 positivity status in tissue sample obtained at diagnosis or relapse
- Received at least two prior treatment which must include at least one intensive systemic therapy.
- Disease progression or relapsed disease within 12 months after autologous stem cell transplant
- ECOG performance score of ≤2 if \>16 years old, or Lansky performance score of \>50 if ≤16 years old at screening
- Has sufficient organ function to tolerate treatment with CAR-T cell therapy
- For women of childbearing potential, a negative pregnancy test prior to apheresis
Exclusion Criteria11
- Patients with active infection
- Patients with B cell ALL post allogeneic transplant with active GVHD or on immunosuppression
- Recent donor lymphocyte infusion (DLI) after allogeneic transplant, less than 6 weeks between DLI and CAR T infusion
- Current autoimmune disease, or history of autoimmune disease with potential CNS involvement
- Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischaemia or haemorrhage, dementia, paralysis)
- Patients who are positive for HBsAg, HCV RNA positive or with HIV infection
- Pulmonary function: Grade 1 dyspnea and pulse oxygenation \> 91% on room air
- Cardiac function: Fractional shortening \<28% or left ventricular ejection fraction \<45% by echocardiography.
- Renal function: Creatinine clearance \<50 mL/min/1.73 m2
- Liver function: Patients with a serum bilirubin \>3 times upper limit of normal or an AST or ALT \> 5 times upper limit of normal, unless due to leukaemic liver infiltration in the estimation of the investigator
- Rapidly progressive disease that in the estimation of the investigator would compromise ability to complete study therapy.
Interventions
anti-CD19 chimeric antigen receptor modified T-cell (CAR-T)
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT06462248