CD123-Directed Autologous T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)

Inclusion Criteria for Procurement and T-cell Production:

Age ≤21 years old
Relapsed/refractory CD123+ disease defined as follows:

AML/MDS

Relapsed disease: Patients developing recurrent disease after a first complete remission (CR)
Refractory disease: Patients not achieving a CR after 2 cycles of induction chemotherapy

B-cell ALL

Relapsed disease that is CD123 positive and CD19 negative/dim or patients otherwise ineligible for CD19 directed therapies including

Patients in 2nd or greater relapse
Patients with relapse after allogeneic HSCT
Refractory disease that is CD123 positive and CD19 negative/dim or patients otherwise ineligible for CD19 directed therapies

T-cell All • Relapsed refractory disease that is CD123 positive

BPDCN

• Relapsed/refractory disease that has failed front-line therapy

Estimated life expectancy of >12 weeks
Karnofsky or Lansky (age-dependent) performance score ≥50
Patients with a history of prior allogeneic HCT must be clinically recovered from prior HCT therapy, have no evidence of active GVHD and have not received a donor lymphocyte infusion (DLI) within the 28 days prior to apheresis
Patient must have an identified, suitable HCT donor
For females of child-bearing age:
Not lactating with intent to breastfeed
Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
Meets eligibility criteria to undergo autologous apheresis, or have previously undergone autologous apheresis

Exclusion Criteria:

Known primary immunodeficiency
History of HIV infection
Severe intercurrent uncontrolled bacterial, viral or fungal infection (e.g. active hepatitis B or C infection or adenovirus infection)
History of hypersensitivity reactions to murine protein-containing products
Patients with acute promyelocytic leukemia (APL, t (15;17))
Known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide.

Inclusion Criteria for Treatment:

Age≤21 years old
Detectable disease that is CD123+ (at least MRD+ disease)
Estimated life expectancy of >8 weeks
Karnofsky or Lansky (age-dependent) performance score≥50
Patients with a history of prior allogeneic HCT must be clinically recovered from prior HCT therapy, have no evidence of active GVHD and have not received a donor lymphocyte infusion (DLI) within the 28 days prior to planned infusion
Patient must have an identified, suitable HCT donor
Adequate cardiac function defined as left ventricular ejection fraction >40%, OR shortening fraction ≥25%
EKG without evidence of clinically significant arrhythmia
Adequate renal function defined as creatinine clearance or radioisotope GFR ≥50 ml/min/1.73m2 (GFR ≥40 ml/min/1.73m2 if < 2 years of age)
Adequate pulmonary function defined as forced vital capacity (FVC)≥50% of predicted value; or pulse oximetry≥92% on room air if patient is unable to perform pulmonary function testing
Total Bilirubin≤3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome
Alanine aminotransferase (ALT) OR aspartate aminotransferase (AST) ≤5 times the upper limit of normal for age
Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy

For females of child-bearing age

Not lactating with intent to breastfeed
Not pregnant with negative serum pregnancy test within 7 days prior to enrollment
If sexually active, agreement to use birth control until 3 months after T- cell infusion. Male partners should use a condom.
Available autologous transduced T-cell product that has met GMP release criteria

Exclusion Criteria:

Known primary immunodeficiency
History of HIV infection
Severe intercurrent uncontrolled bacterial, viral or fungal infection
History of hypersensitivity reactions to murine protein-containing products
History of severe hypersensitivity reactions to cornstarch or hydroxyethyl starch.
Receiving systemic steroids therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone, in the 7 days prior to CD123-CAR T- cell infusion
Receiving systemic therapy in the 14 days prior to CD123-CAR T-cell infusion, which will interfere with the activity of the CD123-CAR T cells in vivo (in the opinion of the study PI(s))
Receiving rituximab therapy in the 30 days prior to CD123-CAR T cell infusion. (This exclusion criterion is intended to prevent premature exposure of CD123-CAR T cells to rituximab, which would activate the safety switch and promote CAR T-cell apoptosis).
Receiving intrathecal chemotherapy in the 7 days prior to CD123-CAR T cell infusion.
Known contraindication to the protocol defined lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide.
Active CNS disease