Phase 2
N=56
A Phase II Study of Crenolanib in Relapsed/Refractory Acute Myeloid Leukemia Patients With FLT3 Activating Mutations
Acute Myeloid Leukemia With FLT3 Activating Mutations That Has Relapsed or Been Refractory After One or More Prior Therapies
Bottom Line
View on ClinicalTrials.gov: NCT01657682 ↗Enrolled (actual)
56
Serious AEs
92.9%
Results posted
Nov 2023
Primary outcome: Primary: Response Rate of Patients Receiving Crenolanib Therapy — 8; 3; 4; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Crenolanib besylate (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Arog Pharmaceuticals, Inc.
- Primary completion
- Apr 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Response Rate of Patients Receiving Crenolanib Therapy |
8; 3; 4; 1; 9; 2 | — |
| SECONDARY Duration of Overall Survival |
237; 100; 85 | — |
| SECONDARY Study Drug Exposure |
57; 43.5; 50 | — |
Summary
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).
Eligibility Criteria
Inclusion Criteria
- Confirmed primary AML relapsed or refractory after prior therapy, AML secondary to antecedent chemotherapy or radiation therapy, or AML due to prior myelodysplastic syndrome (MDS)/ myeloproliferative neoplasm (MPN) as defined by WHO criteria with presence of either FLT3 ITD and/or other FLT3 activating mutations
- Patients with secondary AML should have failed no more than two (2) prior regimens
- Patients with antecedent MDS/MPN, defined by WHO criteria, without any prior therapy for AML, regardless of the number of therapies for MDS/ MPN
- Patients with primary AML should have received no more than two (2) prior cytotoxic containing salvage regimens. Reinduction with the same regimen or stem cell transplant will not be considered a separate salvage regimen. Change of drugs will be considered a salvage regimen. Unlimited FLT3 TKI therapy (even in combination with cytotoxics/hypomethylating agents) is allowed for patients enrolled in cohort B
- Patients must have tested positive for FLT3-ITD and /or other FLT3 activating mutations within 30 day screening period
- Males and females age ≥18 years
- ECOG PS 0-2
- Adequate liver function, defined as bilirubin ≤1.5x ULN, ALT ≤3.0x ULN, and AST ≤3.0x ULN
- Adequate renal function, defined as serum creatinine ≤1.5x ULN
- Recovery from non-hematological toxicities of prior therapy (including HSCT) to no more than grade 1 (except alopecia)
- Subjects should have received no anti-leukemic therapy (except hydroxyurea) prior to the first dose of crenolanib as follows: for 14 days for classical cytotoxic agents and for five times the t1/2 (half-life) for FLT3 inhibitors and antineoplastic agents that are neither cytotoxic nor FLT3 inhibitors (e.g. hypomethylating agent or MEK inhibitor)
- Negative pregnancy test for WOCBP
- Able and willing to provide written informed consent.
Exclusion Criteria
- Absence of a FLT3 activating mutation
- grade 2 persistent non hematological toxicity related to transplant
- Prior crenolanib treatment for a non-leukemic indication
- Major surgical procedures within 14 days of Day 1 administration of crenolanib.
- Unwillingness or inability to comply with protocol.
Data sourced from ClinicalTrials.gov (NCT01657682). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.