PH 2 ADI-PEG 20 Acute Myeloid Leukemia

Study Overview
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Brief Summary
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Certain cancers require the amino acid arginine. Arginine deiminase (ADI) is an enzyme from microbes that degrade arginine. ADI has been formulated with polyethylene glycol and has been used to treat patients that have cancers that require arginine. In this study, the investigators will evaluate the response rate, as determined by the revised International Working Group recommendations.

Official Title
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Phase 2 Study of ADI-PEG 20 in Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: ADI-PEG 20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute myeloid leukemia (AML) diagnosed by morphologic, histochemical or cell surface marker criteria. Patients with AML must have either: (a) relapsed or refractory leukemia after receiving at least one prior conventional induction therapy. Those in early first relapse must not have a matched donor and/or they must not be a candidate for allogeneic stem cell transplantation (usually this would mean the patient is too ill, obese, has a co-morbid condition or is over the age of 55 years) or (b) poor-risk AML as defined below: (i) Treatment related AML, except if it is associated with favorable cytogenetics (e.g., inversion 16, t(16;16), t(8;21), t(15;17), and not a candidate for stem cell transplantation, or (ii) AML with an antecedent hematologic disease (e.g., MDS, myelofibrosis, polycythemia vera, etc.), and not a candidate for stem cell transplantation. (iii) De novo AML > 70 years of age. (iv) AML with unfavorable cytogenetics regardless of age (>18 years), if patients are not candidates for allogeneic transplantation. Unfavorable cytogenetics are the following: complex (>3 abnormalities), -7, -5, 7q-, 5q-, abnormalities of 11q23 excluding t(9;11), t(9;22), inversion 3, t(3;3), t(6;9). (c) Patients older than 60 years of age who had AML (i.e., > 20% bone marrow blasts) and no prior therapy for AML Age ≥ 18 years. ECOG performance status of 0-2. Post-menarche female subjects and male subjects must be asked to use appropriate contraception for both the male and female for the duration of the study. Subjects must agree to use two forms of contraception or agree to refrain from intercourse for the duration of the study. Females must not be pregnant at the start of the study, and a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. Exclusion Criteria: Patients with infections requiring intravenous (IV) antibiotic/antiviral therapy are not eligible for entry onto the study; patients on prophylactic antibiotics or antivirals are acceptable. Pregnancy or lactation. Expected non-compliance. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, psychiatric illness, social situations that would limit compliance with study requirements or DIC. Subjects who have had any anticancer treatment prior to entering the study and have not recovered to baseline (except alopecia) or≤ Grade 1 AEs, or deemed irreversible from the effects of prior cancer therapy. AEs > Grade 1 that are not considered a safety risk by the Sponsor and investigator may be allowed upon agreement with both. Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present in the opinion of the investigator will not affect patient outcome in the setting of current diagnosis.

Ages Eligible for Study
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Minimum Age: 18 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: ADI-PEG 20<br>arginine deiminase formulated with polyethlene glycol | Drug: ADI-PEG 20<br> <br> * Other names: arginine deiminase formulated with polyethylene glycol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate |  | 2 years estimated | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Time on treatment Overall survival Evaluate the response rate and correlate with patient disease burden, and type of disease. Determine the pharmacodynamics of ADI-PEG 20 Determine the immunogenicity of ADI-PEG 20 | 2 years estimated | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Argininosuccinate Synthetase, Arginine, Arginine deiminase, Failed prior systemic therapy