B-ALL Clinical Trial
Official title:
CD123-Directed Autologous T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)
Verified date | August 2023 |
Source | St. Jude Children's Research Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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. 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
Status | Active, not recruiting |
Enrollment | 32 |
Est. completion date | July 1, 2025 |
Est. primary completion date | July 1, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 21 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
United States | St Jude Children's Research Hospital | Memphis | Tennessee |
United States | St. Jude Children's Research Hospital | Memphis | Tennessee |
Lead Sponsor | Collaborator |
---|---|
St. Jude Children's Research Hospital |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 |
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