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

Last updated: January 8, 2019
Sponsor: Arog Pharmaceuticals, Inc.
Overall Status: Trial Not Available

Phase

2

Condition

N/A

Treatment

N/A

Clinical Study ID

NCT03324243
ARO-014
  • Ages 1-21
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Age ≥ 1 years and ≤ 21 years

  2. Confirmed diagnosis of AML according to World Health Organization (WHO) 2016classification

  3. Definitive evidence of a FLT3-ITD and/or FLT3-TKD (D835/I836) mutation at the time ofenrollment

  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 oldand 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

  1. 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

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, Bloomsyndrome, Kostmann syndrome, or Shwachman syndrome)

  • AML secondary to prior MDS/MPN, including chronic myelomonocytic leukemia andjuvenile 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 lymphoblasticleukemia (ETP-ALL)

  1. Patients who are refractory to first line (induction and re-induction) and a secondline (1st salvage) treatment for AML.

  2. Patients who have received more than 1 prior allogeneic HSCT

  3. Patients will be excluded if they have a systemic fungal, bacterial, viral or otherinfection of which they exhibit ongoing signs/symptoms related to the infectionwithout improvement despite appropriate antibiotics or other treatment.

  4. Patients will be excluded if there is a plan to administer non-protocol chemotherapy,radiation therapy, or immunotherapy during the study period.

  5. Known severe liver disease (e.g. cirrhosis, non-alcoholic steatohepatitis, sclerosingcholangitis or hyperbilirubinemia)

  6. Known, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)

  7. Currently receiving prophylactic treatment of hepatitis B with anti-viral therapy

  8. Known infection with human immunodeficiency virus (HIV)

Study Design

Study Start date:
January 01, 2018
Estimated Completion Date:
December 31, 2020