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

• Sponsor: Arog Pharmaceuticals, Inc. (Industry)
• Overall Status: Withdrawn
• CT.gov ID: NCT03324243
• Collaborator: (none)
• Enrollment: 0
• Arm: 1
• Anticipated Duration (Months): 35

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory FLT3-mutated AML	Drug: Crenolanib; Drug: Fludarabine; Drug: Cytarabine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Crenolanib With Fludarabine and Cytarabine in Pediatric Patients With Relapsed/Refractory FLT3-Mutated Acute Myeloid Leukemia
• Anticipated Study Start Date: Jan 1, 2018
• Anticipated Primary Completion Date: Dec 1, 2020
• Anticipated Study Completion Date: Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Crenolanib	Drug: Crenolanib; 66.7 mg/m2 three times a day (TID); Other Names: Crenolanib besylate ; Drug: Fludarabine; 30 mg/m2/day, intravenous infusions over 30 mins.; Drug: Cytarabine; 2000 mg/m2/day, intravenous infusions over 1-3 hours.

Outcome Measures

Primary Outcome Measures

1. Number of patients experiencing ≥ Grade 3 adverse events as assessed by CTCAE v4.0 [From study entry to 30 days post-treatment]

2. Number of patients experiencing Grade 4 adverse events related to crenolanib as assessed by CTCAE v4.0 [60 days]

3. Rate of early mortality [60 days]

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

Secondary Outcome Measures

1. Event-free survival (EFS) [4 years]

   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.

2. Relapse-free survival (RFS) [4 years]

   RFS is defined as the time from the date of remission to date of relapse or death.

3. Overall survival (OS) [4 years]

   OS is defined as the time from the date of start of treatment until death.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

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 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)

1. Patients who are refractory to first line (induction and re-induction) and a second line (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 other infection of which they exhibit ongoing signs/symptoms related to the infection without 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, sclerosing cholangitis 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)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Arog Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Arog Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03324243
• Other Study ID Numbers: ARO-014
• First Posted: Oct 27, 2017
• Last Update Posted: Jan 10, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia, Myeloid, Acute; Cytarabine; Fludarabine; Crenolanib

Study Results

No Results Posted as of Jan 10, 2019