Clinical Trials /

Tagraxofusp in Treating Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm After Stem Cell Transplant

NCT04317781

Description:

This phase II trial studies the side effects of tagraxofusp in treating patients with blastic plasmacytoid dendritic cell neoplasm after stem cell transplant. Tagraxofusp is a type of immunotoxin that is made by linking a protein called IL-3 to a toxic substance. Tagraxofusp may help find cancer cells that express IL-3 and kill them without harming normal cells.

Related Conditions:
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Tagraxofusp in Treating Patients With Blastic Plasmacytoid Dendritic Cell Neoplasm After Stem Cell Transplant
  • Official Title: Tagraxofusp (SL-401) Therapy for Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Patients Post-Autologous or Post-Allogeneic Hematopoietic Cell Transplantation

Clinical Trial IDs

  • ORG STUDY ID: 2018-0646
  • SECONDARY ID: NCI-2019-03832
  • SECONDARY ID: 2018-0646
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT04317781

Conditions

  • Blastic Plasmacytoid Dendritic Cell Neoplasm

Interventions

DrugSynonymsArms
Tagraxofusp-erzsDiphtheria Toxin(388)-Interleukin-3 Fusion Protein, DT(388)-IL3 Fusion Protein, DT388IL3 fusion protein, Elzonris, IL3R-targeting Fusion Protein SL-401, SL-401, TAGRAXOFUSP, Tagraxofusp ERZSTreatment (tagraxofusp-erzs)

Purpose

This phase II trial studies the side effects of tagraxofusp in treating patients with blastic plasmacytoid dendritic cell neoplasm after stem cell transplant. Tagraxofusp is a type of immunotoxin that is made by linking a protein called IL-3 to a toxic substance. Tagraxofusp may help find cancer cells that express IL-3 and kill them without harming normal cells.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To evaluate the safety of tagraxofusp-erzs (tagraxofusp) in patients with blastic
      plasmacytoid dendritic cell neoplasm (BPDCN) after autologous (auto) or allogeneic (allo)
      hematopoietic cell transplantation (HCT).

      SECONDARY OBJECTIVES:

      I. To estimate progression-free survival (PFS) in patients with BPDCN receiving maintenance
      therapy with tagraxofusp after auto-HCT or allo-HCT.

      II. To estimate the overall survival (OS) in patients with BPDCN receiving maintenance
      therapy with tagraxofusp after auto-HCT or allo-HCT.

      OUTLINE:

      Within day 45 and 120 after stem cell transplant, patients receive tagraxofusp-erzs
      intravenously (IV) over 15 minutes on days 1-3 of cycles 1-4 and days 1-2 of subsequent
      cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease
      progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for up to 1 year.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (tagraxofusp-erzs)ExperimentalWithin day 45 and 120 after stem cell transplant, patients receive tagraxofusp-erzs IV over 15 minutes on days 1-3 of cycles 1-4 and days 1-2 of subsequent cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
  • Tagraxofusp-erzs

Eligibility Criteria

        Inclusion Criteria:

          -  Eligible patients will be aged >= 18 years. Pediatric patients age 2 years and older
             will be considered on a case by case basis.

          -  Diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) according to World
             Health Organization (WHO) classification or confirmed by hematopathology

          -  The patients must be in partial response or better

          -  > 30 days post-transplant without active or chronic infections

          -  Karnofsky performance status >= 60%; Lansky >= 60

          -  Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal by
             multigated acquisition (MUGA) scan or echocardiogram within 30 days of first protocol
             treatment

          -  Diffusion capacity of the lung for carbon monoxide (DLCO) > 40% of predicted value
             (corrected for hemoglobin) within 3 months of registration

          -  Forced expiratory volume in 1 second (FEV1) > 40% of predicted value within 3 months
             of registration

          -  Forced vital capacity (FVC) > 40% of predicted value within 3 months of registration

          -  Serum creatinine =< 1.5 mg/dL (133 mmol/L)

          -  Serum albumin >= 3.2 g/dL (or >= 32 g/L) without IV albumin within the previous 72
             hours

          -  Bilirubin =< 1.5 x the upper limit of normal ([ULN] except patients with Gilbert
             syndrome in whom bilirubin level of > 1.5 x ULN will be allowed)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times ULN

          -  Hemoglobin >= 8 g/dL with or without transfusion in the last 7 days

          -  Absolute neutrophil count (ANC) >= 1000 without granulocyte colony stimulating factor
             (GCSF) or granulocyte-macrophage colony-stimulating factor (GMCSF) in the last 2 weeks
             prior to screening

          -  Platelets >= 50,000micro/mL

          -  For allo-HCT, no >= grade 2 visceral (gut or liver) acute graft versus host disease
             (GVHD) and no >= grade 3 or any other acute GVHD (patients with chronic GVHD will be
             allowed at the discretion of the investigator)

          -  Patient agrees to use acceptable contraceptive methods for the duration of time in the
             study, and to continue to use acceptable contraceptive methods for 2 months after the
             last tagraxofusp infusion

          -  Woman of child bearing potential (WOCBP) with a negative serum or urine pregnancy test
             within 14 days of tagraxofusp treatment

          -  Patient or patient's legal representative, parent(s) or guardian able to sign informed
             consent

          -  The patient can adhere to the study visit schedule and other protocol requirements,
             including follow-up for survival assessment

        Exclusion Criteria:

          -  The patient has persistent clinically significant non-hematologic toxicities >= grade
             2 (excluding alopecia, nausea, and fatigue)

          -  Evidence of central nervous system (CNS) involvement

          -  Uncontrolled and active pulmonary disease

          -  Requirement for oxygen treatment

          -  Receiving chemotherapy, radiotherapy or other anti-cancer therapy within 14 days of
             first dose of study drug. There must be at least a 6-week interval from the last
             immunotherapy therapy

          -  Uncontrolled infection

          -  Human immunodeficiency virus (HIV)/hepatitis B and/or C

          -  Any history of invasive malignancy in the last 2 years excluding any malignancy such
             as cervical cancer or skin cancer (excluding melanoma) that is considered cured at the
             time of screening

          -  Pregnant or breast-feeding woman

          -  Patient has uncontrolled intercurrent illness or medical/psychiatric condition that
             would limit compliance with study requirements or that would in the investigator's
             opinion place the patient at an unacceptably high risk for toxicities

          -  Clinical significant cardiopulmonary disease including uncontrolled or New York Heart
             Association (NYHA) class 3 or 4 congestive heart failure, uncontrolled angina,
             uncontrolled hypertension, uncontrolled arrhythmia, myocardial infarction or stroke
             within 6 months of first protocol treatment or corrected QT (QTc) > 480 ms
      
Maximum Eligible Age:N/A
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tolerability of tagraxofusp post-stem cell transplantation (SCT)
Time Frame:Up to 1 year
Safety Issue:
Description:Tolerability is defined as receipt of at least 75% of planned tagraxofusp doses in at least 4 cycles of therapy. The percentage of patients considered 'tolerating' will be presented along with the associated 95% exact confidence interval.

Secondary Outcome Measures

Measure:Progression free survival (PFS)
Time Frame:From treatment start date to date of disease progression or death, assessed up to 1 year
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method. Median PFS as well as rates with corresponding 95% confidence intervals will be presented.
Measure:Overall survival (OS)
Time Frame:From treatment start date to death, assessed up to 1 year
Safety Issue:
Description:Will be estimated using the Kaplan-Meier method. Median OS as well as rates with corresponding 95% confidence intervals will be presented.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

March 19, 2020