A Multiple Dose, Dose Escalation Trial of AEB1102 in Patients With AML or MDS

Study Overview
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Brief Summary
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This is the first study of the safety of increasing dose levels of AEB1102 in patients with Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. The study will also evaluate the amounts of AEB1102 in blood, the effects of AEB1102 on blood amino acid levels and the antitumor effects of AEB1102.

Official Title
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A Phase 2 Dose-Escalation Study of AEB1102 (Co-ArgI-PEG) in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Refractory to Hypomethylating Agents

Conditions
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Myelodysplastic Syndrome, Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Co-ArgI-PEG modified human arginase I


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide informed consent Age 18 and older Diagnosis of AML or MDS according to the WHO criteria AML relapsed or refractory to at least one attempt at induction or subjects not candidates for aggressive induction regimens MDS refractory to treatment with HMA therapy or with recurrence or progression of MDS following a response to an HMA Has adequate organ function: AST and ALT < 3X the ULN, serum bilirubin < 2X the ULN, serum creatinine of < 2 mg/dL, or a calculated creatinine clearance of > 50 mL/minute ECOG Performance Score of 0 -2 Recovered from the effects of any prior systemic therapy, radiotherapy or surgery Willing to use physician approved birth control method Exclusion Criteria: Current CNS Leukemia Acute promyelocytic leukemia or AML with a t(15;17) (q22;q12) cytogenetic abnormality or Bcr/Abl positive leukemia < 60 days from ASCT; has chronic graft-versus host disease (GVHD) or requires continued treatment with systemic immunosuppressive agents Uncontrolled infection Known HIV, hepatitis B or hepatitis C. Other active malignancy that requires therapy If female, is lactating or breast feeding Hypersensitivity to PEG or other component of AEB1102 (Co-ArgI-PEG)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AEB1102 (Co-ArgI-PEG) administered via IV weekly.<br>Co-ArgI-PEG modified human arginase I | Drug: Co-ArgI-PEG modified human arginase I<br> <br> * Other names: AEB1102;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose and Recommended Phase 2 Dose | The dose level at which no more than 1/6 patients experiences dose-limiting toxicity | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety profile (changes in physical exam, laboratory measures, reported adverse events) | changes in physical exam, laboratory measures, reported adverse events | 4 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, MDS