Recruiting

Phase 1

CD123-CAR T-CellCD123-Directed T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)

Sponsor:

St. Jude Children's Research Hospital

Code:

NCT04318678

Conditions

AML/MDS

B-ALL

T-ALL

BPDCN

Eligibility Criteria

Sex: All

Age: 0 - 21

Healthy Volunteers: Not accepted

Interventions

CD123-CAR T

Cyclophosphamide

Fludarabine

Mesna

Rituximab

Study Details

Brief summary:

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.
To determine the safety of an intravenous infusion of escalating doses of donor derived, CD123-CAR T cells in patients (≤21 years) with recurrent/refractory CD123+ disease (AML/MDS, B-ALL, T-ALL, BPDCN or MPAL) 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 therapy
To compare in vivo properties of donor-derived versus autologous CD123- CAR T cells

Conditions

AML/MDS

B-ALL

T-ALL

BPDCN

Study ID

NCT04318678

Start date

Jul 29, 2020

Status verified date

May, 2026

Completion date

Jul 29, 2030

Anticipated

Primary completion date

Jul 29, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 0 - 21

Healthy Volunteers: Not accepted

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 Design

Enrollment

108 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

other: ARM A CD123-CAR T cell therapy

For patients who have not received an allogeneic transplant or for patients who have received allogeneic transplant and do not have a transplant donor available

CD123-CAR T-cell dose and infusion Up to 4 Dose levels will be evaluated with a maximum dose of 2.5 x 10\^8 CAR+ T cells. If dose limiting toxicities (DLTs) are observed on Dose level 1 then the cell dose is de- escalated.

experimental: ARM B CD123-CAR T cell therapy

For patients who relapsed following allogeneic transplant and whose CAR T-cells will be manufactured from the previous transplant donor, when available.

CD123-CAR T-cell dose and infusion Up to 4 Dose levels will be evaluated with a maximum dose of 2.5 x 10\^8 CAR+ T cells. If dose limiting toxicities (DLTs) are observed on Dose level 1 then the cell dose is de- escalated.

Interventions

CD123-CAR T

To treat relapsed/refractory CD123+ AML/MDS, B-ALL, T-ALL or BPDCN patient population that needs new cancer-directed therapies.

Cyclophosphamide

Cyclophosphamide is a nitrogen mustard derivative. It acts as an alkylating agent that causes cross-linking of DNA strands by binding with nucleic acids and other intracellular structures, thus interfering with the normal function of DNA.

Fludarabine

Fludarabine phosphate is a synthetic purine nucleoside analog. It acts by inhibiting DNA polymerase, ribonucleotide reductase and DNA primase by competing with the physiologic substrate, deoxyadenosine triphosphate, resulting in inhibition of DNA synthesis

Mesna

Mesna is a synthetic sulfhydryl (thiol) compound. Mesna contains free sulfhydryl groups that interact chemically with urotoxic metabolites of oxaza-phosphorine derivatives such as cyclophosphamide and ifosfamide

Rituximab

Rituximab is a monoclonal antibody directed against the CD20 antigen on the surface of B-lymphocytes

Primary outcome measure

Maximum tolerated dose of CD123-CAR T cells (CATCHAML) [ Time Frame: 4 weeks after CD123-CAR T-cell infusion ]

Central Contacts and Locations

Central contacts

Swati Naik, MD

888-226-4343 referralinfo@stjude.org

Locations

St Jude Children's Research Hospital

Recruiting

Memphis, Tennessee, United States, 38105

Contacts

Swati Naik, MD

888-226-4343 referralinfo@stjude.org

Principal Investigator:

Swati Naik, MD

St. Jude Children's Research Hospital

Recruiting

Memphis, Tennessee, United States, 38105

Contacts

Paulina Velasquez, MD

888-226-4343 referralinfo@stjude.org

Principal Investigator:

Paulina Velasquez, MD

More Information

Sponsor

St. Jude Children's Research Hospital

Last update posted

May 19, 2026

Last verified

May, 2026

Keywords

CD123+

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by St. Jude Children's Research Hospital on 2026-05-19.