A Phase II Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia
Overview
- Phase
- Phase 2
- Intervention
- Crenolanib
- Conditions
- Relapsed/Refractory FLT3-mutated AML
- Sponsor
- Arog Pharmaceuticals, Inc.
- Primary Endpoint
- Number of patients experiencing ≥ Grade 3 adverse events as assessed by CTCAE v4.0
- Status
- Withdrawn
- Last Updated
- 7 years ago
Overview
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.
Investigators
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 ≥
- •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:
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.
Arms & Interventions
Crenolanib
Intervention: Crenolanib
Crenolanib
Intervention: Fludarabine
Crenolanib
Intervention: Cytarabine
Outcomes
Primary Outcomes
Number of patients experiencing ≥ Grade 3 adverse events as assessed by CTCAE v4.0
Time Frame: 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
Time Frame: 60 days
Rate of early mortality
Time Frame: 60 days
Number of patients who died within 60 days of start of therapy
Secondary Outcomes
- Event-free survival (EFS)(4 years)
- Relapse-free survival (RFS)(4 years)
- Overall survival (OS)(4 years)