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Study to Evaluate the Safety and Clinical Activity of UCART123 in Patients With BPDCN (ABC123)

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ClinicalTrials.gov Identifier: NCT03203369
Recruitment Status : Recruiting
First Posted : June 29, 2017
Last Update Posted : December 20, 2017
Sponsor:
Information provided by (Responsible Party):
Cellectis S.A.

Brief Summary:
A Phase 1 dose-finding study of Universal Chimeric Antigen Receptor T-cells targeting cluster of differentiation (CD) 123 (UCART123) administered intravenously to patients with relapsed or refractory Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN), followed by a dose expansion phase in relapsed or refractory BPDCN patients or newly diagnosed BPDCN patients.

Condition or disease Intervention/treatment Phase
Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Biological: UCART123 Phase 1

Detailed Description:
This is a Phase I, first-in-human, open-label, dose-finding study of UCART123 administered intravenously to patients with BPDCN. he study will consist of two phases, a dose-escalation phase in relapsed or refractory BPDCN patients and a dose-expansion phase in relapsed/refractory and newly diagnosed BPDCN patients and relapsed/refractory BPDCN patients. The safest dose of UCART123 used at the dose level where activity is observed will be used in the dose-expansion phase. The study's primary assessment is the the safety and tolerability of UCART123 administered to patients with BPDCN, and to determine the Recommended Phase 2 Dose (RP2D) of UCART123. T

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1, 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 Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Actual Study Start Date : June 28, 2017
Estimated Primary Completion Date : December 15, 2021
Estimated Study Completion Date : June 15, 2022


Arm Intervention/treatment
Experimental: Part 1: Dose Escalation
A single intravenous administration of UCART123. Dose escalation in Part 1 will include 3 doses ranging from 6.25 x 10^5 cells/kg to 6.25 x 10^6 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 at the RP2D. 2 Cohorts: Patients with Relapsed/Refractory BPDCN and Newly Diagnosed BPDCN.
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 ]
    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-tumor activity [ Time Frame: Between Day 28 and Day 35, then every 3 months during 1 year, then every 6 months for a total of 2 years ]
    Anti-tumor activity following BPDCN composite criteria from 3 sources: 1) Assessment of anti-tumor activity by International Working Group (IWG) criteria for Acute Myeloid Leukemia (AML); 2) Assessment of skin lesions by Modified Severity Weights Assessment Tool (mSWAT); and 3) Assessment of anti-tumor activity using the Lugano criteria.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Main Inclusion Criteria:

  • Patients with a diagnosis BPDCN according to World Health Organization (WHO) classification confirmed by hematopathology;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to enrollment. Within the frame of this study, female patients of childbearing potential and male patients with partners of childbearing potential must use an effective method of birth control, as described below, as well as their partners.

Patients enrolled in the Dose Finding Portion of the Study:

  • Patients ≥18 years and ≤80 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).
  • Patients with histological and/or cytological evidence of BPDCN in the peripheral blood, bone marrow, spleen, lymph nodes, skin, and/or other sites that is persistent/recurrent following prior treatment for BPDCN.

Patients enrolled in the Expansion Phase of the Study:

  • Age ≥18 years
  • Patients with histological and/or cytological evidence of BPDCN in the peripheral blood, bone marrow, spleen, lymph nodes, skin, and/or other sites that is either previously untreated or is persistent/recurrent following prior treatment for BPDCN.

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;
  • Active or previous central nervous system leukemia involvement
  • Presence of active and clinically relevant central nervous system (CNS) disorder;
  • Immunosuppression following a Hematopoietic Stem Cell Transplantation (HSCT) within 6 weeks prior to study entry;
  • Use of rituximab and other anti-cluster of differentiation antigen 20 (CD20) antibodies known to have the same epitope as rituximab or anti-cluster of differentiation antigen 20 (CD20) for which the epitope is unknown within 3 months prior to enrollment;
  • 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;
  • Any known uncontrolled cardiovascular disease, pulmonary embolism, hypertension not adequately controlled by standard medications within 3 months prior to enrollment.
  • 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 ClinicalTrials.gov identifier (NCT number): NCT03203369


Contacts
Contact: Naveen Pemmaraju, MD 713-792-4956 NPemmaraju@mdanderson.org
Contact: Aaron Logue, MBA 513-579-9911 ext 12889 a.logue@medpace.com

Locations
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Cellectis S.A.
Investigators
Study Director: Mathieu Simon, MD Cellectis S.A.

Responsible Party: Cellectis S.A.
ClinicalTrials.gov Identifier: NCT03203369     History of Changes
Other Study ID Numbers: UCART123_02
First Posted: June 29, 2017    Key Record Dates
Last Update Posted: December 20, 2017
Last Verified: December 2017
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.:
Blastic plasmacytoid dendritic cell neoplasm
Natural Killer (NK) cell blastic lymphoma
Hematologic malignancies
Cluster of differentiation (CD) CD4+CD56+ hematodermic tumor
Acute leukemia and myeloid neoplasms
Chimeric Antigen Receptor T-cell (CAR-T) therapy
Allogeneic
Cluster of differentiation 4 (CD4)
Cluster of differentiation 56 (CD56)

Additional relevant MeSH terms:
Neoplasms