Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Central Nervous System Depressants

All Drugs and Chemicals

Antineoplastic Agents

Other Dietary Supplements

Benzocaine

Crenolanib

Tannic Acid

Subjects will take crenolanib 200mg/m2/day divided in three doses daily (preferably every eight hours), taken orally at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who are able to proceed to allogeneic stem cell transplant will be able to resume crenolanib therapy post-transplant in an attempt to maintain remission.

Crenolanib Besylate (CP-868,596-26)

This is a Phase II open label study of crenolanib besylate. This study will enroll subjects with relapsed or refractory AML with FLT3 activating mutations. Prior treatment with other FLT3 TKIs is allowed. Subjects will take crenolanib 200mg/m2/day divided in three doses daily (preferably every eight hours), taken orally at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who are able to proceed to allogeneic stem cell transplant will be able to resume crenolanib therapy post-transplant in an attempt to maintain remission.

Phase II Study of Crenolanib in Subjects With Relapsed/Refractory AML With FLT3 Activating Mutations

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

To determine the response rate to crenolanib.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 but \>5%. Hematologic improvement (HI) response included erythroid response where Hgb increased ≥ 1.5 g/dL, platelet response where platelets increased ≥ 30 x 10\^9/L for patient starting with \>20 x 10\^9/L platelets or increase from \<20 x 10\^9/L to \>20 x 10\^9/L and by at least 100% and neutrophil response where at least 100% increase and an increase \>0.5 x 10\^9/L. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or HI.

Arog Pharmaceuticals, Inc.

Safety data was presented in a comprehensive manner since no formal arms existed as part of the study; patients were only categorized this way during post-study data analyses to determine if there was a potential relationship between their prior TKI exposure and their response to crenolanib therapy.

Participants who had relapsed/refractory AML with FLT3 activating mutations who progressed on one or more prior chemotherapy regimens received either 200mg/m2 /day crenolanib divided in three doses daily or 100mg TID depending on the version of the protocol at the time of their enrolment. (preferably every eight hours), taken orally at least 30 minutes pre or post meal. Crenolanib was taken orally at the abovementioned doses at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who were able to proceed to allogeneic stem cell transplant were able to resume crenolanib therapy post-transplant in an attempt to maintain remission.

All Patients

Participants who had relapsed/refractory AML with FLT3 activating mutations whose leukemia progressed and have a history of prior therapy with one or more FLT3 TKIs received either 200mg/m2 /day crenolanib divided in three doses daily or 100mg TID depending on the version of the protocol at the time of their enrolment. (preferably every eight hours), taken orally at least 30 minutes pre or post meal. Crenolanib was taken orally at the abovementioned doses at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who were able to proceed to allogeneic stem cell transplant were able to resume crenolanib therapy post-transplant in an attempt to maintain remission.

TKI Pre-treated

Participants who had relapsed/refractory AML with FLT3 activating mutations who progressed on one or more prior chemotherapy regimens excluding any FLT3 TKI received either 200mg/m2 /day crenolanib divided in three doses daily or 100mg TID depending on the version of the protocol at the time of their enrolment. (preferably every eight hours), taken orally at least 30 minutes pre or post meal. Crenolanib was taken orally at the abovementioned doses at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who were able to proceed to allogeneic stem cell transplant were able to resume crenolanib therapy post-transplant in an attempt to maintain remission.

TKI Naive

Total

18 to 44 years

45 to 60 years

Greater than 60 years

Age, Customized

Sex: Female, Male

Black or African American

White

Race/Ethnicity, Customized

FLT3-ITD

FLT3-D835

FLT3-ITD and D835

Mutations in the gene encoding the trans-membrane tyrosine kinase FLT3. The type of FLT3 mutation detected by bone marrow assessment at diagnosis was collected. Subjects had either internal tandem duplications (ITD) in the juxtamembrane domain, point mutations or deletions in the tyrosine kinase domain (TKD) or both ITD and TKD mutations together.

FLT3 status

Number of prior therapies

ECOG 0

ECOG 1

ECOG 2

ECOG performance status graded by the investigator during a physical assessment. A greater ECOG grade is associated with greater impact of the disease on the ability of the subject to live. Grade 0 indicates subjects who are fully active and able to carry on all pre-disease performance. Grade 1 indicates subjects restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. Grade 2 indicates subjects who are ambulatory and capable of all selfcare but unable to carry out any work activities.

Spots Global Cancer Trial Database for relapsed or refractory acute myeloid leukemia with flt3 activating mutations