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Tagraxofusp in Patients With CD123+ or With BPDCN-IPh-like Acute Myeloid Leukemia

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: NCT04342962
Recruitment Status : Not yet recruiting
First Posted : April 13, 2020
Last Update Posted : September 18, 2020
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

Brief Summary:

Non-randomized, open-label, multicenter phase II Study for the treatment of

  • 25 R/R BPDCN-IF (CD123/CD4/CD56 positive) AML patients and
  • 25 patients presenting R/R AML CD123+, but negative for either, or both, CD4 and CD56.

Patients will be treated with 12 mcg/kg/day of tagraxofusp for 5 days, for at least 4 cicles.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: tagraxofusp Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Tagraxofusp in Patients With CD123+ or With Blastic Plasmacytoid Dendritic Cell Neoplasm Immunophenotype-like Acute Myeloid Leukemia
Estimated Study Start Date : December 2020
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2025

Arm Intervention/treatment
Experimental: Experimental arm

12 mcg/kg/day of tagraxofusp for 5 days, for at least 4 cycles of therapy; each cycle is 21 days.

Patients will receive the study drug until disease progression or in case of toxicity.

Drug: tagraxofusp
Tagraxofusp is provided as an intravenous (IV) injectable and administered as a 15-minute IV infusion. Cycle 1 will include a 2-day dosing period for the first 3 enrolled patients (Days 1-2), a 2-day plus an optional 3rd day for patients 4-6 (Days 1-2 + Day 3 if patient meets criteria for continued dosing) and a 3-day dosing period for patients 7 and beyond (Days 1-3). Cycle 2 and beyond will include a 5-day dosing period for all patients (Days 1-5). In all cycles and schedules, dose delays up to Day 10 of each cycle will be allowed for resolution of toxicities.

Primary Outcome Measures :
  1. The objective response rate (ORR) [ Time Frame: 4 months ]
    Evaluate the activity of tagraxofusp, in terms of ORR (PR + CR + CRi), in patients with CD123+ or BlasticPlasmacytoid Dendritic Cell Neoplasm-like phenotype (BPDCN-IF) Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML).

Secondary Outcome Measures :
  1. Rate of AEs and SAEs [ Time Frame: 28 months ]
    Safety analysis according to CTCAE criteria

  2. Overall survival (OS) [ Time Frame: 24 months ]
    Overall survival

  3. Event Free Survival (EFS) [ Time Frame: 24 months ]
    Event Free Survival

  4. Disease Free Survival (DFS) [ Time Frame: 24 months from response assessment ]
    Disease Free Survival

  5. Cumulative incidence of relapse (CIR) [ Time Frame: 24 months from response assessment ]
    Cumulative incidence of relapse

  6. Percentage of patients undergoing allogeneic stem cell transplantation [ Time Frame: 12 months ]
    in MRD-negative CR

Information from the National Library of Medicine

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

Inclusion Criteria:

  • The patient has evidence of AML in the peripheral blood and/or bone marrow with either BPDCN-IF [CD123/CD4/CD56 (+)] or with AML that is CD123+ but negative for either, or both, CD4 and CD56.
  • The patient is ≥18 years old.
  • The patient must be refractory to at least one previous line of conventional therapy (either high dose therapy or hypomethylating agents) or relapsed after receiving conventional therapy (a maximum of two previous line of therapy is admitted).
  • The patient has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 to 2.
  • The patient has adequate baseline organ function, including cardiac, renal, and hepatic function:

    1. Left ventricular ejection fraction (LVEF) ≥institutional lower limit of normal as measured by multigated acquisition (MUGA) scan or 2-dimensional (2-D) echocardiography(ECHO) within 21 days before start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG).
    2. Serum creatinine ≤1.5 mg/dL (133 μmol/L).
    3. Serum albumin ≥3.2 g/dL (32 g/L) (albumin infusions are not permitted to enable eligibility).
    4. Bilirubin ≤1.5 mg/dL (26 μmol/L).
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the upper limit of normal (ULN).
  • If the patient is a woman of childbearing potential (WOCBP), she must have a negative serum or urine pregnancy test at screeningwithin 1 week before treatment.
  • The patient has signed informed consent before initiation of any study-specific procedures or treatment.
  • The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment.
  • The patient (male and female) agrees to use acceptable contraceptive methods for the duration of time on the study and continue to use acceptable contraceptive methods for 1 week after the last infusion of tagraxofusp.

Exclusion Criteria:

  • The patient has a diagnosis of acute promyelocytic leukemia (APL; FAB subtype M3).
  • The patient has persistent clinically significant toxicities of Grade≥2 from previous chemotherapy (excluding alopecia, nausea, fatigue, and liver function tests [as mandated in the inclusion criteria]).
  • The patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study entry.
  • The patient has received treatment with an investigational agent within 14 days of study entry.
  • The patient has previously received treatment with tagraxofusp.
  • The patient has an active malignancy and/or cancer history (excluding antecedent MDS) that may confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) with substantial potential for recurrence and/or ongoing active malignancy will be evaluated on a case by case basis. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, cervical intraepithelial neoplasia, organ-confined prostate cancer with no evidence of progressive disease.
  • The patient has clinically significant cardiovascular disease (eg, uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months before study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
  • The patient has uncontrolled, clinically significant pulmonary disease (eg, chronic obstructive pulmonary disease, pulmonary hypertension) that, in the opinion of the Investigator, would put the patient at significant risk for pulmonary complications during the study.
  • The patient has known active or suspected central nervous system (CNS) leukemia. If suspected, CNS leukemia should be ruled out with relevant imaging and/or examination of cerebrospinal fluid.
  • The patient is receiving immunosuppressive therapy - with the exception of low-dose prednisone (≤10 mg/day) - for treatment or prophylaxis of graft-versus-host disease (GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at least 14 days before study treatment and there must be no evidence of Grade ≥2 GVHD.
  • The patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements.
  • The patient is pregnant or breastfeeding.
  • The patient has known positive status for human immunodeficiency virus or active or chronic hepatitis B or hepatitis C (Patients with positive serology for HBV can be enrolled and must receive antiviral prophylaxis - i.e lamivudine or entcavir).
  • The patient is oxygen-dependent.
  • The patient has any medical condition that, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicities.
  • The patient has AML and requires more than 1 g/day of hydroxyurea (Hydroxyureaispermittedatdoses of ≤1 g/day.)

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): NCT04342962

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Contact: Paola Fazi 0670390528
Contact: Enrico Crea 0670390514

Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
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Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto Identifier: NCT04342962    
Other Study ID Numbers: AML2020
First Posted: April 13, 2020    Key Record Dates
Last Update Posted: September 18, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
CD123+ Acute Myeloid Leukemia
Blastic Plasmacytoid Dendritic Cell Leukemia
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type