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Trial record 2 of 19 for:    arog

A Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated 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. Read our disclaimer for details. Identifier: NCT03324243
Recruitment Status : Withdrawn (Withdrawn: Study halted prior to enrollment of first participant)
First Posted : October 27, 2017
Last Update Posted : January 10, 2019
Information provided by (Responsible Party):
Arog Pharmaceuticals, Inc.

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.

Condition or disease Intervention/treatment Phase
Relapsed/Refractory FLT3-mutated AML Drug: Crenolanib Drug: Fludarabine Drug: Cytarabine Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia
Estimated Study Start Date : January 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Experimental: Crenolanib Drug: Crenolanib
66.7 mg/m2 three times a day (TID)
Other Name: Crenolanib besylate

Drug: Fludarabine
30 mg/m2/day, intravenous infusions over 30 mins.

Drug: Cytarabine
2000 mg/m2/day, intravenous infusions over 1-3 hours.

Primary Outcome Measures :
  1. Number of patients experiencing ≥ Grade 3 adverse events as assessed by CTCAE v4.0 [ Time Frame: From study entry to 30 days post-treatment ]
  2. Number of patients experiencing Grade 4 adverse events related to crenolanib as assessed by CTCAE v4.0 [ Time Frame: 60 days ]
  3. Rate of early mortality [ Time Frame: 60 days ]
    Number of patients who died within 60 days of start of therapy

Secondary Outcome Measures :
  1. Event-free survival (EFS) [ Time Frame: 4 years ]
    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.

  2. Relapse-free survival (RFS) [ Time Frame: 4 years ]
    RFS is defined as the time from the date of remission to date of relapse or death.

  3. Overall survival (OS) [ Time Frame: 4 years ]
    OS is defined as the time from the date of start of treatment until death.

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

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Responsible Party: Arog Pharmaceuticals, Inc. Identifier: NCT03324243    
Other Study ID Numbers: ARO-014
First Posted: October 27, 2017    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Leukemia, Myeloid
Fludarabine phosphate
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents