CD123-CAR T-cell therapy for treating acute myeloid leukemia and related conditions

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

This study is testing a new type of T-cell therapy to see if it can safely help young people with certain types of leukemia and related blood disorders.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 108 (estimated)
• Ages: N/A to 21 Years
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (Academic / other)
• Drugs / interventions: rituximab, CAR T, chemotherapy, cyclophosphamide, fludarabine
• Locations: 2 sites (Memphis, Tennessee and 1 other locations)
• Trial ID: NCT04318678 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and maximum tolerated dose of CD123-directed autologous T-cell therapy in patients aged 21 years or younger with recurrent or refractory CD123+ diseases, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and acute lymphoblastic leukemia (ALL). The study consists of two phases: the Collection and Manufacturing Phase, where patients' blood cells are collected and modified, and the Treatment Phase, where patients receive chemotherapy followed by the infusion of the modified T-cells. The trial aims to evaluate both the safety and the anti-leukemia activity of the treatment.

Who should consider this trial

Good fit: Ideal candidates are patients aged 21 years or younger with relapsed or refractory CD123+ AML, MDS, B-ALL, T-ALL, or BPDCN.

Not a fit: Patients with CD123-negative diseases or those who do not meet the age and health criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for young patients with difficult-to-treat forms of leukemia and related conditions.

How similar studies have performed: Other studies using CAR T-cell therapy have shown promising results, indicating potential success for this novel approach.

Eligibility criteria

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

Where this trial is running

Memphis, Tennessee and 1 other locations

• St Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)
• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Swati Naik, MD — St. Jude Children's Research Hospital
• Study coordinator: Swati Naik, MD

Conditions AML/MDS; B-ALL; T-ALL; BPDCN; CD123+