Clinical Trials / Research Studies

Clinical Trials / Research Studies

Who can participate?

Inclusion Criteria:

• Patients with R/R B-ALL who have received commercial tisagenlecleucel and have (an) additional dose(s) available for early reinfusio

• History of CD19 expressing (in peripheral blood or bone marrow by flow cytometry) BALL prior to tisagenlecleucel infusion

• Peripheral blood B-cell aplasia (BCA) within 14 days prior to reinfusion (See section 13.8: B-cell aplasia will be defined as peripheral blood (PB) absolute B lymphocyte count < 50/μL and PB B lymphocyte < 1% of the total lymphocytes)

• Minimal residual disease negative complete remission (CR/CRi) in bone marrow within 14 days prior to reinfusion, including resolution of extramedullary disease

• Patients with tisagenlecleucel that is deemed out of specification (OOS) will be permitted on this protocol if the reason for OOS is deemed to not impact the toxicity and efficacy profile of CAR T cell therapy

• Reasons for product being OOS include cell viability < 80%, total nucleated cell count <2 × 10^9 in leukapheresis product, failed interferon-γ release assay, leukapheresis product collected >9 months prior, and determination of residual beads >50 beads per 3 × 10^6 cells

• Patients age: < 26 years at time of first tisagenlecleucel order placement

• Recovered from severe toxicities following initial dose of tisagenlecleucel

• CRS

• Neurotoxicity/ICANS

• Adequate organ function at time of treatment is required and is defined:

• Hepatic: Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia

• Hepatic: AST and ALT < 5x the upper limit of normal for age, unless thought to be disease-related

• Renal: Serum creatinine <1.5x normal for age. If serum creatinine is outside the normal range, then CrCl > 60 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.72m2 ) >55% of predicted normal for age

Age Mean GFR +/-SD (mL/min/1.73 m2)

• 1 week 40.6 + / - 14.8

• 2 - 8 weeks 65.8 + / - 24.8

• > 8 weeks 95.7 +/- 21.7

• 2 - 12 years 133 +/- 27

• 13 - 21 years (males) 140 +/- 30

• 13 - 21 years (females) 126.0 + / - 22.0 Abbreviations: GFR, glomerular filtration rate; SD, standard deviation. Greater than 2 years old: Normal GFR is 100 mL/ min. Infants: GFR must be corrected for body surface area.

• Cardiac: LVEF ≥ 50% by multi-gated acquisition scan (MUGA), resting echocardiogram, or cardiac magnetic resonance imaging (MRI) within 6 weeks of screening

• Pulmonary: Oxygen saturation as recorded by pulse oximetry of ≥ 90% on room air

• Adequate performance status:

• Age ≥ 16 years: ECOG ≤ 1 or Karnofsky > 60% at treatment

• Age < 16 years: Lansky > 60% at treatment

• Patient must be enrolled on institutional CIBMTR reporting protocol for immune effector cells (IEC)/CAR T cells

• Each patient must be willing to participate as a research subject, and patient or legal guardian must sign an informed consent form, along with patient assent if between 7 to 17 years of age. Legally authorized representatives of adult patients with impaired decision-making capacity will also be able to sign consent.

• Adequate renal, liver, cardiac, and central nervous system (CNS) function

Exclusion Criteria:

• Patients with R/R B-ALL who have received commercial tisagenlecleucel and have (an) additional dose(s) available for early reinfusion

• History of CD19 expressing (in peripheral blood or bone marrow by flow cytometry) BALL prior to tisagenlecleucel infusion

• Peripheral blood B-cell aplasia (BCA) within 14 days prior to reinfusion (See section 13.8: B-cell aplasia will be defined as peripheral blood (PB) absolute B lymphocyte count < 50/μL and PB B lymphocyte < 1% of the total lymphocytes)

• Minimal residual disease negative complete remission (CR/CRi) in bone marrow within 14 days prior to reinfusion, including resolution of extramedullary disease

• Patients with tisagenlecleucel that is deemed out of specification (OOS) will be permitted on this protocol if the reason for OOS is deemed to not impact the toxicity and efficacy profile of CAR T cell therapy

• Reasons for product being OOS include cell viability < 80%, total nucleated cell count <2 × 10^9 in leukapheresis product, failed interferon-γ release assay, leukapheresis product collected >9 months prior, and determination of residual beads >50 beads per 3 × 10^6 cells

• Patients age: < 26 years at time of first tisagenlecleucel order placement

• Recovered from severe toxicities following initial dose of tisagenlecleucel

• CRS

• Neurotoxicity/ICANS

• Adequate organ function at time of treatment is required and is defined:

• Hepatic: Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia

• Hepatic: AST and ALT < 5x the upper limit of normal for age, unless thought to be disease-related

• Renal: Serum creatinine <1.5x normal for age. If serum creatinine is outside the normal range, then CrCl > 60 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.72m2 ) >55% of predicted normal for age

Age Mean GFR +/-SD (mL/min/1.73 m2)

• 1 week 40.6 + / - 14.8

• 2 - 8 weeks 65.8 + / - 24.8

• > 8 weeks 95.7 +/- 21.7

• 2 - 12 years 133 +/- 27

• 13 - 21 years (males) 140 +/- 30

• 13 - 21 years (females) 126.0 + / - 22.0 Abbreviations: GFR, glomerular filtration rate; SD, standard deviation. Greater than 2 years old: Normal GFR is 100 mL/ min. Infants: GFR must be corrected for body surface area.

• Cardiac: LVEF ≥ 50% by multi-gated acquisition scan (MUGA), resting echocardiogram, or cardiac magnetic resonance imaging (MRI) within 6 weeks of screening

• Pulmonary: Oxygen saturation as recorded by pulse oximetry of ≥ 90% on room air

• Adequate performance status:

• Age ≥ 16 years: ECOG ≤ 1 or Karnofsky > 60% at treatment

• Age < 16 years: Lansky > 60% at treatment

• Patient must be enrolled on institutional CIBMTR reporting protocol for immune effector cells (IEC)/CAR T cells

• Each patient must be willing to participate as a research subject, and patient or legal guardian must sign an informed consent form, along with patient assent if between 7 to 17 years of age. Legally authorized representatives of adult patients with impaired decision-making capacity will also be able to sign consent.