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

NCT03324243 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: ARO-014
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Relapsed/Refractory FLT3-mutated AML

Outcome Measures

Primary Outcomes (3)

• Number of patients experiencing ≥ Grade 3 adverse events as assessed by CTCAE v4.0

  From study entry to 30 days post-treatment

• Number of patients experiencing Grade 4 adverse events related to crenolanib as assessed by CTCAE v4.0

  60 days

• Rate of early mortality

  Number of patients who died within 60 days of start of therapy

  60 days

Secondary Outcomes (3)

• Event-free survival (EFS)

  4 years

• Relapse-free survival (RFS)

  4 years

• Overall survival (OS)

  4 years

Study Arms (1)

Crenolanib

EXPERIMENTAL

Drug: Crenolanib; Drug: Fludarabine; Drug: Cytarabine

Interventions

Crenolanib DRUG

66.7 mg/m2 three times a day (TID)

Also known as: Crenolanib besylate

Crenolanib

Fludarabine DRUG

30 mg/m2/day, intravenous infusions over 30 mins.

Crenolanib

Cytarabine DRUG

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

Crenolanib

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Arog Pharmaceuticals, Inc.: lead

MeSH Terms

Conditions

Recurrence

Interventions

crenolanib; fludarabine; Cytarabine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2017
• First Posted: October 27, 2017
• Study Start: January 1, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: January 10, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share