Acute Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia Recurrent, Acute Lymphoblastic Leukemia Refractory, Acute Lymphoblastic Leukemia Not Having Achieved Remission, Acute Lymphoblastic Leukemia With Failed Remission
Conditions
Keywords
CAR-T, MB-CART19.1, ALL, acute lymphoblastic leukemia, relapsed acute lymphoblastic leukemia, refractory acute lymphoblastic leukemia
Brief summary
Single-arm, prospective, open-label feasibility study evaluating the technical and operational feasibility of manufacturing autologous CD19-directed CAR-T cells (MB-CART19.1) at the point of care for the treatment of relapsed or refractory B-ALL in pediatric and adult patients.
Interventions
GENETICMB-CART19.1
All participants will undergo leukapheresis for collection of autologous T cells, which will then be manufactured into MB-CART19.1 on-site using CliniMACS Prodigy platform. Successfully manufactured MB-CART19.1 products will be infused back to the patient following a lymphodepleting chemotherapy regimen.
Sponsors
King Hussein Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 1 year as long as if deemed fit by treating investigator * CD19 expression must be detected (≥20%) on the malignant cells by flow cytometry. * Patients with relapsed or refractory disease with \>5% blasts in the bone marrow after at least one frontline and one salvage chemotherapy regimen. For patients with Philadelphia-positive disease, a second generation or higher TKI must have been utilized in one of the treatment lines. * Patients who have relapsed post alloSCT at least 100 days post-transplant, with no evidence of active graft vs host disease, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment. * Estimated life expectancy \> 12 weeks * Karnofsky or Lansky (age dependent) performance score ≥ 60 * Patients and/or parents must give their written informed consent/assent. * CNS and/or testicular involvement are allowed, only if cleared and in the presence of systemic involvement.
Exclusion criteria
* Rapidly progressive, uncontrolled disease as assessed by the treating physician and/or principal investigator. * Persistent extramedullary disease. * Isolated CNS and/or testicular disease. * Current autoimmune disease, or history of autoimmune disease with potential CNS involvement * Active hepatitis B, C or HIV * Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis) * History of an additional malignancy (≤ 3 years) other than non-melanoma skin cancer or carcinoma in situ. * Pulmonary function: Patients with pre-existing severe lung disease (FEV1 or FVC \< 65%) or an oxygen requirement of \>28% O2 FiO2 or active pulmonary infection. * Cardiac function: Left ventricular ejection fraction \<50% by echocardiography * Renal function: Creatinine clearance \<50 mL/min/1.73 m2 * Liver function: patients with serum bilirubin ≥3 times upper limit of or AST or ALT \> 5 times upper limit of normal, unless due to leukemic liver infiltration as determined by the investigators. * Pregnant or breast-feeding females * Medications: systemic chemotherapies, corticosteroids with the exception of physiologic replacement dosing (\<0.5 mg/kg/day of methylprednicone), tyrosine kinase inhibitors (TKI) within 7 days prior to leukapheresis, Fludarabine/clofarabine or immunosuppressive drugs and antibodies (e.g. rituximab, blinatumomab) or investigational drugs or donor lymphocyte
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of enrolled patients for whom MB-CART19.1 product is successfully manufactured on-site and meets release criteria. | From patient enrollment through completion of manufacturing and release testing; estimated 2-4 weeks per patient and up to 12 months for the full cohort. | Assessment of the feasibility and success rate of on-site manufacturing of MB-CART19.1, defined as the proportion of enrolled patients whose cell product is produced and meets established release specifications. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) (CR, CR with incomplete hematologic recovery (CRh)) on day 28. | Up to approximately 28 days after the last patient infusion. | Evaluation of overall response rate (ORR) at Day 28, measured as the percentage of patients who achieve complete remission (CR) or complete remission with incomplete hematologic recovery (CRh) following MB-CART19.1 infusion. |
| Duration of response time from first documented response to progression or death up to 12 months post-infusion | Up to 12 months post-infusion | Duration of response time from first documented response to progression or death up to 12 months post-infusion |
| Rate of measurable residual disease (MRD) negativity at 1-, 3-, 6- and 12-month intervals | at 1-, 3-, 6- and 12-month intervals | Evaluation of rate of measurable residual disease (MRD) negativity at scheduled follow-up visits to monitor clinical status and response post-infusion. |
| MB-CART19.1 manufacturing turnaround time | From leukapheresis to product release (estimated 2 weeks per patient). | Time required to complete on-site manufacturing of MB-CART19.1 from leukapheresis to product release. |
| Overall incidence and severity of adverse events | From infusion through 12 months post-infusion per patient. | Assessment of the overall incidence and severity of adverse events (AEs) in patients receiving MB-CART19.1, including all treatment-related and non-treatment-related events, graded according to standard toxicity criteria. |
| Overall incidence and severity of MB-CART19.1- specific adverse events (cytokine release syndrome (CRS)) | From infusion through 12 months post-infusion per patient. | Assessment of the overall incidence and severity of cytokine release syndrome (CRS) in patients receiving MB-CART19.1, graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria. |
| Overall incidence and severity MB-CART19.1-specific adverse events (Immune effector cell associated neurotoxicity syndrome (ICANS)) | From infusion through 12 months post-infusion per patient. | Assessment of the overall incidence and severity of Immune effector cell associated neurotoxicity syndrome (ICANS) in patients receiving MB-CART19.1, graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria. |
Countries
Jordan
Contacts
CONTACTDr. Zaid Abdel Rahman, Consultant,Hematology/Oncology
CONTACTDr. Hasan Hashem, Consultant,Hematology/Oncology
PRINCIPAL_INVESTIGATORDr Zaid Abdel Rahman, Consultant,Hematology/Oncology
King Hussein Cancer Center
PRINCIPAL_INVESTIGATORDr. Hasan Hashem, Consultant,Hematology/Oncology
King Hussein Cancer Center
Outcome results
None listed