MB-CART19.1 in Relapsed/Refractory Acute Lymphoblastic Leukemia

Official title

MB-CART19.1 in Patients With Relapsed/Refractory CD19-positive B Cell Acute Lymphoblastic Leukemia: A Feasibility Study

Overview

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

• Genetic MB-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.

Primary outcome measures

• Proportion of enrolled patients for whom MB-CART19.1 product is successfully manufactured on-site and meets release criteria. [Time frame: 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.]

Secondary outcome measures (7)

• Overall response rate (ORR) (CR, CR with incomplete hematologic recovery (CRh)) on day 28. [Time frame: Up to approximately 28 days after the last patient infusion.]
• Duration of response time from first documented response to progression or death up to 12 months post-infusion [Time frame: Up to 12 months post-infusion]
• Rate of measurable residual disease (MRD) negativity at 1-, 3-, 6- and 12-month intervals [Time frame: at 1-, 3-, 6- and 12-month intervals]
• MB-CART19.1 manufacturing turnaround time [Time frame: From leukapheresis to product release (estimated 2 weeks per patient).]
• Overall incidence and severity of adverse events [Time frame: From infusion through 12 months post-infusion per patient.]
• Overall incidence and severity of MB-CART19.1- specific adverse events (cytokine release syndrome (CRS)) [Time frame: From infusion through 12 months post-infusion per patient.]
• Overall incidence and severity MB-CART19.1-specific adverse events (Immune effector cell associated neurotoxicity syndrome (ICANS)) [Time frame: From infusion through 12 months post-infusion per patient.]

Eligibility criteria

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 0.01% or higher blasts in the bone marrow, or patients with confirmed disease progression as demonstrated by FDG PET-CT or CT/MRI of the affected lymph node or spleen after at least 2 cycles/lines of chemotherapy are eligible for enrollment. 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Jordan · 1 center

• King Hussein Cancer Center — Amman

Identifiers

NCT: NCT07371403 · 25KHCC164

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗