Overview
CD123-Directed Autologous T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)
Status:
Recruiting
Recruiting
Trial end date:
2025-07-01
2025-07-01
Target enrollment:
0
0
Participant gender:
All
All
Summary
The CD123-CAR T-cell therapy is a new treatment that is being investigated for treatment of AML, T-ALL, B-ALL or 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, 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 cells - To characterize the cytokine profile in the peripheral blood and CSF after treatment with CD123-CAR T cells - To characterize tumor cells post CD123-CAR T-cell therapyPhase:
Phase 1Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
St. Jude Children's Research HospitalTreatments:
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Mesna
Rituximab
Criteria
Inclusion Criteria for Procurement and T-cell Production:- Age ≤21 years old
- Relapsed/refractory CD123+ disease defined as follows:
AML
- 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 Tcells 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