Clinical Trials /

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

NCT04318678

Description:

The CD123+ CAR therapy is a new treatment that is being investigated for treatment of AML. The purpose of this study is to find the maximum (highest) dose of CD123+ CAR cells that is safe to give patients with AML. This would include studying the side effects of the chemotherapy, as well as the CD123+ CAR 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+ AML 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 AML blasts post CD123-CAR T-cell therapy

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CD123-Directed Autologous T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)
  • Official Title: CD123-Directed Autologous T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)

Clinical Trial IDs

  • ORG STUDY ID: CATCHAML
  • NCT ID: NCT04318678

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
CD123-CAR TCD123+CD123+ CAR therapy
CyclophosphamideCytoxanCD123+ CAR therapy
FludarabineFludaraCD123+ CAR therapy
MesnaCD123+ CAR therapy
RituximabRituxanCD123+ CAR therapy

Purpose

The CD123+ CAR therapy is a new treatment that is being investigated for treatment of AML. The purpose of this study is to find the maximum (highest) dose of CD123+ CAR cells that is safe to give patients with AML. This would include studying the side effects of the chemotherapy, as well as the CD123+ CAR 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+ AML 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 AML blasts post CD123-CAR T-cell therapy

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 is the "Treatment Phase".

      The Collection and Manufacturing Phase refers to your blood cells being collected and
      possibly frozen, via a process called apheresis. These cells will then be changed to improve
      their ability to recognize and kill cancer cells.

      The Treatment Phase refers to the portion of the study in which you receive an infusion of
      the CD123+ CAR cells that were made in the Collection and Manufacturing Phase; chemotherapy
      is often given for several days prior to the cellular infusion. You are then monitored for
      any possible side effects.

      Chemotherapy is typically given to get your body ready to accept the CATCHAML treatment.

      Treatment Schedule:

      Patients will receive lymphodepleting chemotherapy followed by infusion of CD123-CAR T cells

      Fludarabine on day -4, -3 and -2

      Cyclophosphamide on day -2

      REST DAY on day -1

      CD123+CAR cell infusion on day 0 or +1
    

Trial Arms

NameTypeDescriptionInterventions
CD123+ CAR therapyOtherCD123-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.
  • CD123-CAR T
  • Cyclophosphamide
  • Fludarabine
  • Mesna
  • Rituximab

Eligibility Criteria

        Inclusion Criteria for Procurement and T-cell Production:

          -  Age ≤21 years old

          -  Relapsed/refractory CD123+ AML defined as follows:

          -  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

          -  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 for Procurement and T-cell Production:

          -  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 with CD123-CAR T cells:

          -  Age≤21 years old

          -  Detectable disease that is CD123+ (at least MRD+ disease defined as <5% blasts by
             morphologic examination of the bone marrow AND ≥0.1% blasts by flow cytometry and/or
             >10^-4 by PCR)

          -  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)≤5times the upper
             limit of normal for age

          -  Hemoglobin >7 g/dl (can be transfused)

          -  Platelet count >20,000/μL (can be transfused)

          -  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

          -  Agreement to participate in long-term follow-up for patients, who have received
             genetically modified cell products (GENEFU)

        Exclusion Criteria for Treatment with CD123-CAR T cells:

          -  Known primary immunodeficiency

          -  History of HIV infection

          -  Severe intercurrent uncontrolled bacterial, viral or fungal infection

          -  History of hypersensitivity reactions to murine protein-containing products

          -  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.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of CD123-CAR T cells (CATCHAML)
Time Frame:4 weeks after CD123 CAR T-cell infusion
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:St. Jude Children's Research Hospital

Last Updated

March 20, 2020