A Phase 1 Study of AMV564 in Patients With Intermediate or High-Risk Myelodysplastic Syndromes
- Conditions
- Myelodysplastic Syndrome (MDS)
- Interventions
- Drug: AMV564 14-Day CIV
- Registration Number
- NCT03516591
- Lead Sponsor
- Amphivena Therapeutics, Inc.
- Brief Summary
An open label, Phase 1, study of AMV564 as monotherapy to assess the safety and efficacy in patients with Myelodysplastic Syndromes
- Detailed Description
A dose-escalation with expansion study of AMV564 (T cell engager) as monotherapy in patients with intermediate-2 or high-risk Myelodysplastic Syndromes
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 14
- ≥ 18 years of age
- Diagnosis of MDS according to WHO 2016 criteria
- ECOG performance status of 0 or 1
- Intermediate-2 or high-risk disease per IPSS
- Fewer than 20% blasts in the bone marrow or peripheral blood
- Disease that is refractory to or relapsed from either a hypomethylating agent (e.g. decitabine or azacitidine) or a standard AML-type intensive regimen
- Adequate organ function
- Prior allogeneic transplant performed ≥ 3 months prior to first dose of AMV564 is allowed provided there is no evidence of active graft-versus-host disease (GVHD) and the patient has been off immunosuppressive therapy for ≥ 4 weeks.
- History of, or known, central nervous system (CNS) disease involvement, or prior history of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade ≥ 3 drug-related CNS toxicity
- Prior allogeneic transplant if performed < 3 months prior to first dose of AMV564, if patient has active GVHD, or if patient has not been off immunosuppressive
- Prior treatment with a therapeutic agent targeting CD33 (e.g. gemtuzumab ozogamicin, SGN-CD33A or AMG 330).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation (3+3 design) AMV564 14-Day CIV A 3 + 3 design, with dose-escalation of AMV564, up to a Maximum Tolerated Dose (MTD) level. AMV564 will be tested as a 14-Day CIV regimen (14-Day Continuous Intravenous Infusion Regimen). Dose Expansion AMV564 14-Day CIV Following determination of the MTD of AMV564, the study will expand at the MTD or a dose level lower than the MTD to obtain initial estimates of response rates and additional information on safety.
- Primary Outcome Measures
Name Time Method Dose limiting toxicity (Dose Escalation) DLTs will be evaluated through 28 days for the 14-Day Continuous Intravenous Infusion Infusion regimen, and 35 days for the Intermittent Intravenous Dosing regimen Dose limiting toxicity to be measured by AEs and SAEs by dose level
Overall Response Rate (Dose Expansion) The treatment period will extend from initiation of AMV564 treatment until the Safety Follow Up visit (30 days after the end of infusion), or response assessment of the last induction cycle, whichever occurs later. Overall response rate (ORR), defined as the proportion of patients who achieve a CR, marrow CR or PR by IWG criteria. Point estimates for ORR, along with the approximate lower 1-sided 90% confidence intervals, will be calculated.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (5)
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Washington University, Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States