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

NCT04318678 | Recruiting Phase 1 FDA Drug

• 1 other identifier: CATCHAML
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 2

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

Keywords

CD123+

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of CD123-CAR T cells (CATCHAML)

  A phase I design to determine the maximum tolerated dose (MTD) of autologous, CD123- CAR T cells. Four dose levels (3x10\^5/kg, 1x10\^6/kg, 3x10\^6/kg, and 1x10\^7/kg) will be evaluated.

  4 weeks after CD123-CAR T-cell infusion

Study Arms (2)

ARM A CD123-CAR T cell therapy

OTHER

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.

Drug: CD123-CAR T; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna; Drug: Rituximab

ARM B CD123-CAR T cell therapy

EXPERIMENTAL

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.

Drug: CD123-CAR T; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna; Drug: Rituximab

Interventions

CD123-CAR T DRUG

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

Also known as: CD123-CAR T cells

ARM A CD123-CAR T cell therapy; ARM B CD123-CAR T cell therapy

Cyclophosphamide DRUG

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.

Also known as: Cytoxan

ARM A CD123-CAR T cell therapy; ARM B CD123-CAR T cell therapy

Fludarabine DRUG

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

Also known as: Fludara

ARM A CD123-CAR T cell therapy; ARM B CD123-CAR T cell therapy

Mesna DRUG

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

ARM A CD123-CAR T cell therapy; ARM B CD123-CAR T cell therapy

Rituximab DRUG

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

Also known as: Rituxan

ARM A CD123-CAR T cell therapy; ARM B CD123-CAR T cell therapy

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (2)

St Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Mesna; Rituximab

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Histiocytic Disorders, Malignant; Lymphoma; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Swati Naik, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

• Paulina Velasquez, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Swati Naik, MD

CONTACT

866-278-5833; referralinfo@stjude.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Due to review of dose limiting toxicity.

Study Record Dates

• First Submitted: March 20, 2020
• First Posted: March 24, 2020
• Study Start: July 29, 2020
• Primary Completion (Estimated): July 29, 2029
• Study Completion (Estimated): July 29, 2030
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (2)