A Study to Evaluate Lanraplenib (LANRA) in Combination With Gilteritinib in Participants With FLT3-mutated Relapsed or Refractory Acute Myeloid Leukemia (AML)
Study Details
Study Description
Brief Summary
The primary objective of this study is to evaluate the safety of lanraplenib (LANRA) in combination with the FMS-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib, in participants with relapsed or refractory (R/R) FLT3-mutated acute myeloid leukemia (AML).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: Dose Escalation Sequential cohorts of participants will receive escalating doses of lanraplenib (LANRA) once daily (QD) + gilteritinib QD in each 28 day cycle for determination of the maximally tolerated dose (MTD) / recommended Phase 2 dose (RP2D) of LANRA in combination with gilteritinib. |
Drug: Lanraplenib
Orally via tablets
Other Names:
Drug: Gilteritinib
Orally via tablets
Other Names:
|
| Experimental: Part 2: Expansion Cohort Following identification of the maximally tolerated dose (MTD) / recommended Phase 2 dose (RP2D) of lanraplenib (LANRA) in combination with gilteritinib in Part 1, an expansion cohort will enroll. The expansion cohort will receive LANRA in combination with gilteritinib at the MTD / RP2D once daily (QD) in each 28 day cycle. |
Drug: Lanraplenib
Orally via tablets
Other Names:
Drug: Gilteritinib
Orally via tablets
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Part 1 and Part 2: Number of Participants who Experience a Treatment-Emergent Adverse Event (TEAE) [Cycle 1 Day 1 through 30 days after last dose (up to approximately 5 years; cycle is 28 days)]
- Part 1 and Part 2: Number of Participants who Experience a Dose-Limiting Toxicity (DLT) for Lanraplenib (LANRA) [Cycle 1 Day 1 through pre-dose Cycle 2 Day 1 (cycle is 28 days)]
- Part 1: Maximally Tolerated Dose (MTD) of Lanraplenib (LANRA) [Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)]
- Part 1: Recommended Phase 2 Dose (RP2D) of Lanraplenib (LANRA) [Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)]
Secondary Outcome Measures
- Part 1: Maximal Plasma Concentration (Cmax) of Lanraplenib (LANRA) [Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)]
- Part 1: Time to Maximal Plasma Concentration (Tmax) of Lanraplenib (LANRA) [Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)]
- Part 1: Area Under the Plasma Concentration x Time Curve from Hour 0 to the Last Measurable Time Point (AUC0-last) of Lanraplenib (LANRA) [Cycle 1 Day 1 through Cycle 2 Day 1 (cycle is 28 days)]
- Part 1 and Part 2: Composite Complete Response (CR) Rate [Up to 5 years]
- Part 1 and Part 2: Composite Complete Response (CR) with Partial Hematologic Recovery (CRh) [Up to 5 years]
- Part 1 and Part 2: Duration of Response (DoR) [Up to 5 years]
- Part 1 and Part 2: Event Free Survival (EFS) [Up to 5 years]
- Part 1 and Part 2: Overall Survival (OS) [Up to 5 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adults ≥18 years of age with acute myeloid leukemia (AML) and at least 1 prior line of therapy
-
FMS-like tyrosine kinase 3 (FLT3)-mutated disease documented in a local reference laboratory
-
Have the ability to understand the requirements and procedures of the study and sign a written informed consent form
-
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2
-
Adequate hepatic and renal function
-
Prothrombin time (PT), activated partial thromboplastin time (aPTT) and international normalized ratio (INR) ≤1.5x upper limit of normal (ULN) unless receiving therapeutic anticoagulation
-
Negative serum ß-human chorionic gonadotropin (HCG) test in women of child-bearing potential (WOCBP)
-
Left ventricular ejection fraction ≥50% confirmed by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan
Exclusion Criteria:
-
Known central nervous system (CNS) involvement with leukemia
-
Clinical signs/symptoms of leukostasis that have failed therapy including hydroxyurea and/or leukapheresis of at least 3 days duration
-
Pregnant or breastfeeding women
-
Active infection with hepatitis B, C or human immunodeficiency virus (HIV) infection
-
Disseminated intravascular coagulation with active bleeding or signs of thrombosis
-
Known active coronavirus disease 2019 (COVID-19)
-
Administration of a live attenuated virus vaccine within 35 days before Cycle 1 Day 1 (C1D1)
-
History of non-myeloid malignancy except for the following: adequately treated localized basal cell or squamous cell carcinoma of the skin; cervical carcinoma in situ; superficial bladder cancer; asymptomatic prostate cancer without known metastatic disease, with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for > 1 year prior to start of study therapy; or any other cancer that has been in complete remission without treatment for ≥3 years prior to enrollment
-
Clinically significant heart disease
-
Prolongation of the congenital long measure between Q wave and T wave in the electrocardiogram (QT) interval at baseline
-
Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection at the time of study treatment initiation
-
Current (within 30 days of study enrollment) drug-induced liver injury, chronic active hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis, primary biliary cholangitis with inadequate response to ursodeoxycholic acid or other health authority approved therapy, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, orportal hypertension
-
Ongoing (within 6 weeks of study enrollment) hepatic encephalopathy
-
Ongoing immunosuppressive therapy, including systemic chemotherapy for treatment of leukemia
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California Los Angeles (UCLA) | Los Angeles | California | United States | 990095 |
| 2 | The Blood and Marrow Transplant Group of Georgia | Atlanta | Georgia | United States | 30342 |
| 3 | Texas Oncology - Baylor Charles A. Sammons Cancer Center | Dallas | Texas | United States | 75246 |
| 4 | Froedtert Hospital | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Kronos Bio
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KB-LANRA- 1001
- 2022-001279-15