Study Evaluating Safety and Efficacy of UCART123 in Patients With Acute Myeloid Leukemia (AML123)

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. Identifier: NCT03190278
Recruitment Status : Recruiting
First Posted : June 16, 2017
Last Update Posted : March 22, 2018
Information provided by (Responsible Party):
Cellectis S.A.

Brief Summary:
Phase I, first-in-human, open-label, dose-finding study of UCART123 administered intravenously to patients with Acute Myeloid Leukemia (AML), followed by a dose-escalation stage in Relapsed or Refractory AML patients and a dose expansion stage in Relapsed/Refractory AML patients, and in poor-prognosis, newly diagnosed AML patients in the European LeukemiaNet (ELN) Adverse genetic risk group.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Biological: UCART123 Phase 1

Detailed Description:
This study's primary objective is to assess the safety and efficacy of Universal Chimeric Antigen Receptor (CAR) T-cells targeting Cluster of Differentiation (CD) 123 (UCART123) administered to patients with relapsed/refractory and newly diagnosed high-risk acute myeloid leukemia (AML), and to determine the Recommended Phase 2 Dose (RP2D) of UCART123. The primary benefit expected from UCART123 for participating patients is a high degree of T-cell expansion that could induce high and sustained anti-CD123 activity, leading to durable remission in poor-prognosis patients with AML. Also, patients are expected to benefit from the immediate availability of UCART123 cells and the higher, more homogenous transduction success rate expected from healthy allogeneic cells, compared to autologous T-cells. The absence of cell-surface expression of the TCR complex on UCART123 eliminates the TCR-recognition of histocompatibility antigens, the primary mechanism of GVHD, and confers a "universal" character to UCART123, which circumvents the necessity of human leukocyte antigen (HLA) matching between donor and recipient.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 156 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I, Open Label Dose Escalation and Dose Expansion Study to Evaluate the Safety, Expansion, Persistence, and Clinical Activity of a Single Dose of UCART123 (Allogeneic Engineered T Cells Expressing Anti-CD123 Chimeric Antigen Receptor), Administered in Patients With Relapsed/Refractory Acute Myeloid Leukemia, and Patients With Newly Diagnosed High-risk Acute Myeloid Leukemia
Actual Study Start Date : June 19, 2017
Estimated Primary Completion Date : June 15, 2021
Estimated Study Completion Date : December 15, 2021

Arm Intervention/treatment
Experimental: Part 1: Dose Escalation
A single IV administration of UCART123 in the dose escalation phase will explore 3 doses of UCART123 ranging from 6.25x10^5 cells/kg to 6.25 x10^6 cells/kg and continue until the Recommended Phase 2 Dose (RP2D) is identified.
Biological: UCART123
Allogeneic engineered T-cells expressing anti-CD123 Chimeric Antigen Receptor given as a single dose following a lymphodepleting regimen

Experimental: Part 2: Dose Expansion
A single intravenous administration of UCART123. 2 Cohorts: Relapsed and Refractory AML and newly diagnosed AML in the ELN adverse genetic risk group.
Biological: UCART123
Allogeneic engineered T-cells expressing anti-CD123 Chimeric Antigen Receptor given as a single dose following a lymphodepleting regimen

Primary Outcome Measures :
  1. Incidence, nature, and severity of adverse events and serious adverse events [ Time Frame: Through Day 84 (+/- 7 days), dose limiting toxicities are assessed up to 42 days after UCART123 infusion ]
    Adverse events assessed according to common terminology criteria for adverse events (CTCAE v4.03); cytokine release syndrome (CRS); tumor lysis syndrome (TLS); graft vs. host disease (GvHD)

Secondary Outcome Measures :
  1. Assessment of Anti-leukemic activity [ Time Frame: Day 14, between Day 28 and Day 35, then every 3 months for one year and every 6 months during the second year after treatment ]
    Anti-leukemic activity, as measured by International Working Group (IWG) criteria for AML response criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Main Inclusion Criteria:

  • AML Blast cell expressing CD123 by flow cytometry performed as per standard practice
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • Adequate organ function.
  • Estimated life expectancy >12 weeks
  • Adequate organ function, including renal and hepatic function based on the last assessment performed within the Screening Period

Patients enrolled in the Dose Finding Portion of the Study:

  • Patients ≥18 and ≤75 years old with relapsed or primary refractory acute myeloid leukemia.
  • Patients enrolled onto the dose-finding phase of the study must have an identified donor and transplant strategy prior to initiation of the lymphodepletion regimen.

Patients enrolled in the Expansion Phase of the Study: Relapsed/Refractory Cohort

• Patients ≥18 years old with relapsed or primary refractory acute myeloid leukemia.

Patients Enrolled in the Dose-Escalation Phase of the Study •Patients ≥18 years and ≤75 years old (The 3 first patients at Dose Level 1 will be <65 years old. Enrollment of patients ≥ 65 years old must be approved by the DSMB after the completion of cohort 1)

Newly Diagnosed Cohort

• Patients with newly diagnosed, untreated Acute Myeloid Leukemia (as defined by World Health Organization (WHO) criteria,) who meet criteria for the European Leukemia Net (ELN) Adverse genetics prognostic group.

Eligibility criteria for UCART123 administration

  • No uncontrolled infections;
  • Afebrile (<38°C per CTCAE v4.03);
  • Normal organ function since eligibility screening, and no new clinical or laboratory findings that, in the opinion of the investigator, might jeopardize the patient's safety
  • Off all but replacement dose of corticosteroids from Day -7 to Day 28 (replacement dose is the patient's individualized dose defined for physiological replacement).

Main Exclusion Criteria:

  • Previous treatment with investigational gene or chimeric antigen receptor therapy.
  • Acute Promyelocytic Leukemia
  • Active or previous central nervous system leukemia involvement
  • Presence of active and clinically relevant Central Nervous System (CNS) disorder
  • Use of rituximab and other anti-cluster of differentiation 20 (CD20) antibodies known to have the same epitope as rituximab or anti-CD20 for which the epitope is unknown within 3 months prior to start of lymphodepletion
  • Patients may not receive ≥ 20 mg of prednisone or equivalent between days -7 and +28 of UCART123 infusion. Hydrocortisone required for mineralocorticoid replacement therapy is authorized at all times as needed clinically. Topical, inhaled, or nasal route of steroids are permitted;
  • Known infection with Human Immunodeficiency Virus (HIV) or Human T-lymphotropic Virus 1 (HTLV-1).
  • A known hypersensitivity to any of the test materials or related compounds including murine and bovine products;
  • Any known uncontrolled cardiovascular disease;
  • Active bacterial, fungal or viral infection not controlled by adequate treatment, at enrollment

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 identifier (NCT number): NCT03190278

Contact: Gabrielle Gosciniak (646) 962-9359
Contact: Aaron Logue, MBA 513-579-9911 ext 12889

United States, New York
Weill Cornell Medical College Recruiting
New York, New York, United States, 10065
Contact: Gail Roboz, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Cellectis S.A.
Study Director: Mathieu Simon, MD Cellectis S.A.

Responsible Party: Cellectis S.A. Identifier: NCT03190278     History of Changes
Other Study ID Numbers: UCART123_01
First Posted: June 16, 2017    Key Record Dates
Last Update Posted: March 22, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Cellectis S.A.:
Acute Myeloid Leukemia
Relapsed/Refractory Acute Myeloid Leukemia
Newly diagnosed AML
ELN adverse genetic risk group
Chimeric Antigen Receptor T-Cell (CAR-T) therapy

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type