Anti-CD19 Chimeric Antigen Receptor Modified T-cell (CAR-T) Therapy for Treatment of B-cell Hematological Malignancies

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 Criteria:

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 criteria of both cohorts

* 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.

Conditions3

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