Status:
RECRUITING
CD123-Directed T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)
Lead Sponsor:
St. Jude Children's Research Hospital
Conditions:
AML/MDS
B-ALL
Eligibility:
All Genders
Up to 21 years
Phase:
PHASE1
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 dend...
Detailed Description
This study will evaluate the safety and maximum tolerated dose of CD123-CAR T cells. This study contains 2 phases. The first part is the called the "Collection and Manufacturing Phase" and the second...
Eligibility Criteria
Inclusion
- 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
Exclusion
Key Trial Info
Start Date :
July 29 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
July 29 2030
Estimated Enrollment :
108 Patients enrolled
Trial Details
Trial ID
NCT04318678
Start Date
July 29 2020
End Date
July 29 2030
Last Update
October 23 2025
Active Locations (2)
Enter a location and click search to find clinical trials sorted by distance.
1
St Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
2
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105