NCT05456269

A Study of Bisantrene Combined With Cytarabine or With Decitabine for Adult Subjects With Extramedullary AML and MDS

An Open-label Two Strata Study of Bisantrene in Combination With Cytarabine Arabinoside or Bisantrene in Combination With Oral Decitabine/Cedazuridine for the Treatment of Acute Myeloid Leukemia Patients With Extramedullary Disease

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Race Oncology Ltd · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a two strata Phase 1b study to assess the safety and efficacy of bisantrene (RC110) in combination with a) cytarabine arabinoside (Ara-C) treatment for patients with relapsed or refractory (R/R) Acute Myeloid Leukemia (AML) with extramedullary disease and able to tolerate intensive chemotherapy; b) in combination with decitabine/cedazuridune (ASTX727) new or relapsed or refractory AML or high risk MDS or CMML with extramedullary disease and unable or not willing to have intensive chemotherapy.

Detailed description

The study is a multicenter, open label in patients with haematological malignancy / myeloproliferative disease (AML, MDS and CMML) and extramedullary disease (EMD) investigating 2 treatment regimens: 1. Stratum 1 will investigate use of high dose intravenous (IV) bisantrene (RC110) in combination with IV Ara-C for R/R AML with EMD able to tolerate intensive chemotherapy. This includes a run-in stage to confirm the dose of bisantrene (RC110) for induction and in combination with Ara-C for consolidation cycles and an expansion and an expansion stage that will treat additional patients at the confirmed bisantrene dose for induction and in combination with Ara-C consolidation cycles; 2. Stratum 2 will investigate use lower doses intravenous (IV) bisantrene (RC-110) in combination with fixed-dose oral decitabine/cedazuridine (ASTX727) to determine the maximum tolerated dose (MTD) for new or R/R AML and HR-MDS/CMML unable to tolerate intensive chemotherapy. Pre-screening will be conducted to identify patients with EMD diagnosed by standard clinical practice including histology and by fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F FDG-PET/CT) imaging.

Conditions

• Acute Myeloid Leukemia
• Recurrent Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia
• Higher Risk Myelodysplastic Syndrome
• Chronic Myelomonocytic Leukemia

Interventions

Type	Name	Description
DRUG	Bisantrene Dihydrochloride (high dose)	Induction monotherapy cycle: IV bisantrene daily on Days 1 to 7, starting at 250 mg/m2 then adjusted to either 275 mg/m2 or 225 mg/m2 based on confirmed dose (Run-in) Consolidation combination cycle/s: IV bisantrene daily on Days 1 to 2
DRUG	Bisantrene Dihydrochloride (low dose)	IV bisantrene at escalating doses for 3 dose levels of 50, 65, 85 mg/m2 on Days 3 and 5 until Maximum tolerated dose (MTD) reached.
DRUG	Cytarabine Hydrochloride	Consolidation cycles: continuous IV cytarabine (100mg/m2) on Days 1 to 5
DRUG	Decitabine and cedazuridine	PO fixed-dose decitabine/cedazuridine 35/100 mg tablet daily for 5 days (Days 1 to 5), 1 hour prior bisantrene infusion

Timeline

• Start date: 2022-07-29
• Primary completion: 2023-08-31
• Completion: 2023-08-31
• First posted: 2022-07-13
• Last updated: 2023-10-03

Locations

1 site across 1 country: Australia