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

Description

The CD123-CAR T-cell therapy is a new treatment that is being investigated for treatment of AML/myelodysplastic syndrome (MDS), T- or B- acute lymphoblastic leukemia (ALL) or blastic plasmacytoid dendritic cell neoplasia (BPDCN). The purpose of this study is to find the maximum (highest) dose of CD123-CAR T cells that is safe to give to these patients. This would include studying the side effects of the chemotherapy, as well as the CD123-CAR T-cell product on the recipient's body, disease and overall survival. Primary Objective To determine the safety of one intravenous infusion of escalating doses of autologous, CD123-CAR T cells in patients (≤21 years) with recurrent/refractory CD123+ disease (AML/MDS, B-ALL, T-ALL or BPDCN) after lymphodepleting chemotherapy. Secondary Objectives To evaluate the antileukemia activity of CD123-CAR T cells. Exploratory Objectives * To assess the immunophenotype, clonal structure and endogenous repertoire of CD123-CAR T cells and unmodified T cel

Trial Eligibility

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

Study Info

Interventions

Locations Recruiting

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