search
Back to results

A Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia

Primary Purpose

Relapsed/Refractory FLT3-mutated AML

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Crenolanib
Fludarabine
Cytarabine
Sponsored by
Arog Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/Refractory FLT3-mutated AML

Eligibility Criteria

1 Year - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥ 1 years and ≤ 21 years
  2. Confirmed diagnosis of AML according to World Health Organization (WHO) 2016 classification
  3. Definitive evidence of a FLT3-ITD and/or FLT3-TKD (D835/I836) mutation at the time of enrollment
  4. Patients must have histologically or molecularly confirmed relapsed or refractory AML
  5. Karnofsky or Lansky performance score ≥ 50. Use Karnofsky for patients > 16 years old and Lansky for patients ≤ 16 years of age.

  6. Adequate renal function, defined as:

    • Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or
    • Normal serum creatinine based on age/gender

  7. Adequate liver function, defined as:

    • Serum total bilirubin ≤ 1.5x ULN for age,
    • Serum aspartate aminotransferase (AST) ≤ 3.0x ULN for age, and
    • Serum alanine aminotransferase (ALT) ≤ 3.0x ULN for age.

Exclusion Criteria:

  1. Patients with any of the following current or previous diagnoses:

    • Acute promyelocytic leukemia (APL)
    • Down syndrome
    • DNA fragility or bone marrow failure syndromes (such as Fanconi anemia, Bloom syndrome, Kostmann syndrome, or Shwachman syndrome)
    • AML secondary to prior MDS/MPN, including chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia
    • Blastic plasmacytoid dendritic cell neoplasm
    • Acute leukemia of ambiguous lineage
    • B-lymphoblastic leukemia/lymphoma
    • T-lymphoblastic leukemia/lymphoma, including early T-cell precursor lymphoblastic leukemia (ETP-ALL)
  2. Patients who are refractory to first line (induction and re-induction) and a second line (1st salvage) treatment for AML.
  3. Patients who have received more than 1 prior allogeneic HSCT
  4. Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection of which they exhibit ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
  5. Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
  6. Known severe liver disease (e.g. cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis or hyperbilirubinemia)
  7. Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
  8. Currently receiving prophylactic treatment of hepatitis B with anti-viral therapy
  9. Known infection with human immunodeficiency virus (HIV)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Crenolanib

    Arm Description

    Outcomes

    Primary Outcome Measures

    Number of patients experiencing ≥ Grade 3 adverse events as assessed by CTCAE v4.0
    Number of patients experiencing Grade 4 adverse events related to crenolanib as assessed by CTCAE v4.0
    Rate of early mortality
    Number of patients who died within 60 days of start of therapy

    Secondary Outcome Measures

    Event-free survival (EFS)
    EFS is defined as the time from the date of start of treatment to the date of failure to achieve a remission, relapse, or death from any cause.
    Relapse-free survival (RFS)
    RFS is defined as the time from the date of remission to date of relapse or death.
    Overall survival (OS)
    OS is defined as the time from the date of start of treatment until death.

    Full Information

    First Posted
    October 18, 2017
    Last Updated
    January 8, 2019
    Sponsor
    Arog Pharmaceuticals, Inc.
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT03324243
    Brief Title
    A Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia
    Official Title
    A Phase II Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2019
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Withdrawn: Study halted prior to enrollment of first participant
    Study Start Date
    January 2018 (Anticipated)
    Primary Completion Date
    December 2020 (Anticipated)
    Study Completion Date
    December 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Arog Pharmaceuticals, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a phase II, multicenter, single-arm study to assess the safety and feasibility of combining crenolanib with fludarabine and cytarabine chemotherapy in pediatric patients with relapsed/refractory FLT3-mutated AML. Patients will receive up to two courses of salvage chemotherapy with fludarabine, cytarabine, and crenolanib. Response will be assessed between day 29-43 of each course.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Relapsed/Refractory FLT3-mutated AML

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Crenolanib
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Crenolanib
    Other Intervention Name(s)
    Crenolanib besylate
    Intervention Description
    66.7 mg/m2 three times a day (TID)
    Intervention Type
    Drug
    Intervention Name(s)
    Fludarabine
    Intervention Description
    30 mg/m2/day, intravenous infusions over 30 mins.
    Intervention Type
    Drug
    Intervention Name(s)
    Cytarabine
    Intervention Description
    2000 mg/m2/day, intravenous infusions over 1-3 hours.
    Primary Outcome Measure Information:
    Title
    Number of patients experiencing ≥ Grade 3 adverse events as assessed by CTCAE v4.0
    Time Frame
    From study entry to 30 days post-treatment
    Title
    Number of patients experiencing Grade 4 adverse events related to crenolanib as assessed by CTCAE v4.0
    Time Frame
    60 days
    Title
    Rate of early mortality
    Description
    Number of patients who died within 60 days of start of therapy
    Time Frame
    60 days
    Secondary Outcome Measure Information:
    Title
    Event-free survival (EFS)
    Description
    EFS is defined as the time from the date of start of treatment to the date of failure to achieve a remission, relapse, or death from any cause.
    Time Frame
    4 years
    Title
    Relapse-free survival (RFS)
    Description
    RFS is defined as the time from the date of remission to date of relapse or death.
    Time Frame
    4 years
    Title
    Overall survival (OS)
    Description
    OS is defined as the time from the date of start of treatment until death.
    Time Frame
    4 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    1 Year
    Maximum Age & Unit of Time
    21 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥ 1 years and ≤ 21 years Confirmed diagnosis of AML according to World Health Organization (WHO) 2016 classification Definitive evidence of a FLT3-ITD and/or FLT3-TKD (D835/I836) mutation at the time of enrollment Patients must have histologically or molecularly confirmed relapsed or refractory AML Karnofsky or Lansky performance score ≥ 50. Use Karnofsky for patients > 16 years old and Lansky for patients ≤ 16 years of age. Adequate renal function, defined as: Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or Normal serum creatinine based on age/gender Adequate liver function, defined as: Serum total bilirubin ≤ 1.5x ULN for age, Serum aspartate aminotransferase (AST) ≤ 3.0x ULN for age, and Serum alanine aminotransferase (ALT) ≤ 3.0x ULN for age. Exclusion Criteria: Patients with any of the following current or previous diagnoses: Acute promyelocytic leukemia (APL) Down syndrome DNA fragility or bone marrow failure syndromes (such as Fanconi anemia, Bloom syndrome, Kostmann syndrome, or Shwachman syndrome) AML secondary to prior MDS/MPN, including chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia Blastic plasmacytoid dendritic cell neoplasm Acute leukemia of ambiguous lineage B-lymphoblastic leukemia/lymphoma T-lymphoblastic leukemia/lymphoma, including early T-cell precursor lymphoblastic leukemia (ETP-ALL) Patients who are refractory to first line (induction and re-induction) and a second line (1st salvage) treatment for AML. Patients who have received more than 1 prior allogeneic HSCT Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection of which they exhibit ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period. Known severe liver disease (e.g. cirrhosis, non-alcoholic steatohepatitis, sclerosing cholangitis or hyperbilirubinemia) Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) Currently receiving prophylactic treatment of hepatitis B with anti-viral therapy Known infection with human immunodeficiency virus (HIV)

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    A Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia

    We'll reach out to this number within 24 hrs