Relapsed/Refractory FLT3-mutated AML Clinical Trial
Official title:
A Phase II Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia
| NCT number | NCT03324243 |
| Other study ID # | ARO-014 |
| Secondary ID | |
| Status | Withdrawn |
| Phase | Phase 2 |
| First received | |
| Last updated | |
| Start date | January 2018 |
| Est. completion date | December 2020 |
| Verified date | January 2019 |
| Source | Arog Pharmaceuticals, Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | December 2020 |
| Est. primary completion date | December 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 1 Year to 21 Years |
| Eligibility |
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) |
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Arog Pharmaceuticals, Inc. |
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of patients experiencing = Grade 3 adverse events as assessed by CTCAE v4.0 | From study entry to 30 days post-treatment | ||
| Primary | Number of patients experiencing Grade 4 adverse events related to crenolanib as assessed by CTCAE v4.0 | 60 days | ||
| Primary | Rate of early mortality | Number of patients who died within 60 days of start of therapy | 60 days | |
| Secondary | Event-free survival (EFS) | 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. | 4 years | |
| Secondary | Relapse-free survival (RFS) | RFS is defined as the time from the date of remission to date of relapse or death. | 4 years | |
| Secondary | Overall survival (OS) | OS is defined as the time from the date of start of treatment until death. | 4 years |