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

Launched by ST. JUDE CHILDREN'S RESEARCH HOSPITAL · Mar 20, 2020

Keywords

ClinConnect Summary

The CATCHAML clinical trial is testing a new treatment called CD123-CAR T-cell therapy for young patients (up to 21 years old) with certain types of blood cancers, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and acute lymphoblastic leukemia (ALL). The main goal of the study is to find out how much of this therapy can be safely given to patients after they receive chemotherapy to prepare their bodies for the treatment. Researchers will also look at how well the therapy works in fighting the cancer and what side effects it may cause.

To be eligible for this trial, patients must be 21 years old or younger and have a specific type of cancer that is still present after previous treatments. They should also have a life expectancy of more than 8 weeks, and their overall health should be stable enough to tolerate the therapy. Participants can expect to receive an infusion of their own modified T-cells, which are a type of white blood cell that helps fight cancer. Throughout the study, doctors will monitor the patients closely for any side effects and to see how well the treatment is working. It's important to note that patients must meet certain health criteria and have an appropriate donor if they have previously undergone a stem cell transplant.

Gender

ALL

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