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Hydroxyurea

Crenolanib

Will enroll relapsed/refractory AML patients with FLT3 activating mutations who progressed on one or more prior chemotherapy regimens excluding any FLT3 TKI.

Will enroll relapsed/refractory AML patients with FLT3 activating mutations whose leukemia has progressed and have history of prior therapy with one or more FLT3 TKIs.

Crenolanib besylate, 100 mg TID, taken orally at least 30 minutes pre- or post- meal. Patients will complete a daily diary to record the date, time and amount (number of tablets) of crenolanib taken and eating schedule.

Concurrent hydroxyurea (maximum 5g total daily dose x 14 days) is permitted during the first 28 days of study therapy.

Crenolanib besylate

Jorge Cortes, MD

This pilot Phase II study is designed to evaluate the efficacy and tolerability of crenolanib in two cohorts of AML patients with FLT3 activation mutations (patients whose leukemia has recurred after prior chemotherapy not including a FLT3 TKI and patients whose leukemia has progressed after prior therapy with a FLT3 TKI).

This is a Phase II open label study of crenolanib besylate. This study will enroll subjects with relapsed acute myeloid leukemia (AML) with FLT3 activating mutations. Two cohorts of patients will be enrolled: those whose AML has recurred after prior chemotherapy without a FLT3 TKI, and those whose AML has progressed after prior therapy with FLT3 TKIs. Subjects will take Crenolanib besylate at 100 mg TID until disease progression, death, or unacceptable toxicities. Concurrent hydroxyurea is permitted during the first 28 days of study therapy.

A Phase II Study of Crenolanib in Relapsed/Refractory Acute Myeloid Leukemia Patients With FLT3 Activating Mutations

To determine the response rate to crenolanib. CR Complete remission (CR) response criteria include a post-baseline bone marrow (BM) biopsy or aspiration % blasts \<5%, absolute neutrophil count (ANC) \>1×10\^9/L and platelet count \>100×10\^9/L. CRi response included all CR criteria met, except participant did not experience either platelet recovery or ANC recovery. Partial Response (PR) response included a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline to a post-baseline result between 5% to 25% in the bone marrow aspirate or biopsy. Blast reduction (BR) response included a decrease of ≥50% in % blasts. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or MLFS.

To determine the overall survival of AML patients with activating FLT3 mutations treated with crenolanib

To determine the study drug exposure of relapse/refractory AML patients receiving 100 mg crenolanib besylate tablets three times daily.

Arog Pharmaceuticals, Inc.

Participants who had relapsed/refractory AML with FLT3 activating mutations who progressed on one or more prior chemotherapy regimens received 100 mg crenolanib besylate tablets administered orally three times a day.

All Patients

Participants who had relapsed/refractory AML with FLT3 activating mutations who progressed on one or more prior chemotherapy regimens excluding any FLT3 TKI received 100 mg crenolanib besylate tablets administered orally three times a day.

Cohort A - No Prior FLT3 TKI Exposure

Participants who had relapsed/refractory AML with FLT3 activating mutations whose leukemia progressed and have history of prior therapy with one or more FLT3 TKIs received 100 mg crenolanib besylate tablets administered orally three times a day.

Cohort B - Prior Therapy With FLT3 TKI

Participants who had relapsed/refractory AML with FLT3 activating mutations whose leukemia progressed and have history of antecedent hematological disorder received 100 mg crenolanib besylate tablets administered orally three times a day.

Cohort C - Antecedent Hematological Disorder

Total

Between 18 and 44 years

Between 45 and 60 years

>60 years

Age, Customized

Sex: Female, Male

Race

Race data was not available for one patient in cohort B.

Race/Ethnicity, Customized

Ethnicity

FLT3-ITD only

FLT3-TKD only

FLT3-ITD and FLT3-TKD

Baseline FLT3 mutation

0 - Normal activity

1 - Symptoms but ambulatory

2 - In bed < 50% of time

Baseline ECOG Performance

Number of Prior Therapies

Edward McDonald

CR/CRi

ORR (CR+PR)

Clinical Benefit (CR+PR+BR)

Resistant disease (RD)

Response Rate of Patients Receiving Crenolanib Therapy

Duration of Overall Survival

Participants who had relapsed/refractory AML with FLT3 activating mutations whose leukemia progressed on one or more prior chemotherapy regimens excluding any FLT3 TKI received 100 mg crenolanib besylate tablets administered orally three times a day.

Participants who had relapsed/refractory AML with FLT3 activating mutations whose leukemia progressed on one or more prior chemotherapy regimens and have history of prior therapy with one or more FLT3 TKI received 100 mg crenolanib besylate tablets administered orally three times a day.

Participants who had relapsed/refractory AML with FLT3 activating mutations whose leukemia progressed on one or more prior chemotherapy regimens and have history of antecedent hematological disorder received 100 mg crenolanib besylate tablets administered orally three times a day.

Spots Global Cancer Trial Database for crenolanib besylate