Clinical Trials /

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

NCT04342962

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tagraxofusp in Patients With CD123+ or With BPDCN-IPh-like Acute Myeloid Leukemia
  • Official Title: Tagraxofusp in Patients With CD123+ or With Blastic Plasmacytoid Dendritic Cell Neoplasm Immunophenotype-like Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: AML2020
  • NCT ID: NCT04342962

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
tagraxofuspExperimental arm

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Experimental armExperimental12 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.
  • tagraxofusp

Eligibility Criteria

        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.)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The objective response rate (ORR)
Time Frame:4 months
Safety Issue:
Description: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

Measure:Rate of AEs and SAEs
Time Frame:28 months
Safety Issue:
Description:Safety analysis according to CTCAE criteria
Measure:Overall survival (OS)
Time Frame:24 months
Safety Issue:
Description:Overall survival
Measure:Event Free Survival (EFS)
Time Frame:24 months
Safety Issue:
Description:Event Free Survival
Measure:Disease Free Survival (DFS)
Time Frame:24 months from response assessment
Safety Issue:
Description:Disease Free Survival
Measure:Cumulative incidence of relapse (CIR)
Time Frame:24 months from response assessment
Safety Issue:
Description:Cumulative incidence of relapse
Measure:Percentage of patients undergoing allogeneic stem cell transplantation
Time Frame:12 months
Safety Issue:
Description:in MRD-negative CR

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Gruppo Italiano Malattie EMatologiche dell'Adulto

Trial Keywords

  • CD123+ Acute Myeloid Leukemia
  • Blastic Plasmacytoid Dendritic Cell Leukemia
  • Relapsed
  • Refractory

Last Updated

April 10, 2020