NCT03318016

Arsenic Trioxide With Cyclophosphamide in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Phase I Trial of Arsenic Trioxide With Cyclophosphamide in Patients With Relapsed/Refractory Acute Myeloid Leukemia

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 5 (actual)
• Sponsor: University of Colorado, Denver · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

Determine the maximum tolerated dose (MTD) and toxicity profile of the combination of cyclophosphamide and ATO (Arsenic Trioxide) in subjects with relapsed refractory AML. Determine the efficacy of ATO and cyclophosphamide in this population, as defined by response rate, response duration, event-free survival (EFS) and overall survival (OS). Determine the number of transplant-eligible subjects who are successfully bridged to stem cell transplantation or donor lymphocyte infusion.

Detailed description

This is an open label phase 1 study of fixed dose ATO (Arsenic Trioxide) and escalating doses of cyclophosphamide using a standard 3+3 dose escalation design. All subjects will be treated with sequential cycles of 3 days of ATO at 0.15 mg/kg/d IV followed by Cyclophosphamide as a single IV dose on day 4 along with mesna at a dose equal to the cyclophosphamide (for doses ≥1000 mg/m2) and hydration for a maximum of 6 cycles. ATO and Cyclophosphamide will be repeated every 28-42 days. Treatment will be given inpatient for the first cycle, with the option of outpatient treatment for subsequent cycles. Subjects may remain on study in the absence of disease progression or unacceptable toxicity for a maximum six cycles. Toxicity assessments will be performed continuously; DLT determination will be made based on adverse events (AEs) that occur during cycle 1 (day 1-28). An expansion cohort of ten subjects at the maximum tolerated dose will occur at the conclusion of dose escalation.

Conditions

• Acute Myeloid Leukemia
• Relapsed/Refractory Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Cyclophosphamide 500 MG	ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 500 mg/m2 on day 4 as a single IV dose along with hydration for a maximum of 6 doses
DRUG	Cyclophosphamide 1000 MG	Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 1000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses
DRUG	Cyclophosphamide 2000 MG	Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 2000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses
DRUG	Cyclophosphamide 3000 MG	Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 3000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses
DRUG	Cyclophosphamide 4000 MG	Enrolled subjects will receive 3 consecutive days of ATO at a fixed dose of 0.15 mg/kg/d IV followed by Cyclophosphamide 4000 mg/m2on day 4 as a single IV dose along with Mesna (in subjects receiving ≥1000mg/m2 Cy) and hydration for a maximum of 6 doses

Timeline

• Start date: 2017-12-15
• Primary completion: 2020-01-15
• Completion: 2021-01-20
• First posted: 2017-10-23
• Last updated: 2024-08-01
• Results posted: 2024-08-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study