Clinical trial NCT03324243: 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
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Relapsed/Refractory FLT3-mutated AML
Lead sponsor: Arog Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-10-27
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Number of patients experiencing ≥ Grade 3 adverse events as assessed by CTCAE v4.0
timeFrame: From study entry to 30 days post-treatment
measure: Number of patients experiencing Grade 4 adverse events related to crenolanib as assessed by CTCAE v4.0
timeFrame: 60 days
measure: Rate of early mortality
timeFrame: 60 days
Secondary outcomes:
measure: Event-free survival (EFS)
timeFrame: 4 years
measure: Relapse-free survival (RFS)
timeFrame: 4 years
measure: Overall survival (OS)
timeFrame: 4 years
Other outcomes:
Locations:
Study officials:
References: