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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04318678
Recruitment Status : Recruiting
First Posted : March 24, 2020
Last Update Posted : June 2, 2020
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Brief Summary:

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

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: CD123-CAR T Drug: Cyclophosphamide Drug: Fludarabine Drug: Mesna Drug: Rituximab Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CD123-Directed Autologous T-Cell Therapy for Acute Myelogenous Leukemia (CATCHAML)
Actual Study Start Date : May 27, 2020
Estimated Primary Completion Date : July 1, 2024
Estimated Study Completion Date : July 1, 2025


Arm Intervention/treatment
CD123+ CAR therapy
CD123-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.
Drug: CD123-CAR T
To treat relapsed/refractory CD123+ AML patient population that needs new cancer-directed therapies.
Other Name: CD123+

Drug: Cyclophosphamide
Cyclophosphamide is a nitrogen mustard derivative. It acts as an alkylating agent that causes cross-linking of DNA strands by binding with nucleic acids and other intracellular structures, thus interfering with the normal function of DNA.
Other Name: Cytoxan

Drug: Fludarabine
Fludarabine phosphate is a synthetic purine nucleoside analog. It acts by inhibiting DNA polymerase, ribonucleotide reductase and DNA primase by competing with the physiologic substrate, deoxyadenosine triphosphate, resulting in inhibition of DNA synthesis
Other Name: Fludara

Drug: Mesna
Mesna is a synthetic sulfhydryl (thiol) compound. Mesna contains free sulfhydryl groups that interact chemically with urotoxic metabolites of oxaza-phosphorine derivatives such as cyclophosphamide and ifosfamide

Drug: Rituximab
Rituximab is a monoclonal antibody directed against the CD20 antigen on the surface of B-lymphocytes
Other Name: Rituxan




Primary Outcome Measures :
  1. Maximum tolerated dose of CD123-CAR T cells (CATCHAML) [ Time Frame: 4 weeks after CD123 CAR T-cell infusion ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04318678


Contacts
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Contact: Paulina Velasquez, MD 866-178-5833 referralinfo@stjude.org

Locations
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United States, Tennessee
St. Jude Children's Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Paulina Velasquez, MD    866-278-5833    referralinfo@stjude.org   
Principal Investigator: Paulina Velasquez, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
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Principal Investigator: Paulina Velasquez, MD St. Jude Children's Hospital
Additional Information:
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Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT04318678    
Other Study ID Numbers: CATCHAML
First Posted: March 24, 2020    Key Record Dates
Last Update Posted: June 2, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data will be made available at the time of article publication.
Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Rituximab
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological