A phase 1 study of SGN-CD123Ain patients with relapsed or refractory acute myeloid leukemia (AML)
The goal of this clinical research study is to find the highest tolerable dose of the study drug SGN-CD123A that can be given to patients with AML. The safety of this drug will also be studied. Researchers also want to learn about any effects the drug may have on AML. This is the first study using SGN-CD123A in humans.
Disease Group: Malignant neoplasms stated as primary lymphoid haematopoietic
Treatment Agent: SGN-CD123A
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Seattle Genetics, Inc
Primary Objective To evaluate the safety and tolerability of SGN-CD123A and to identify the maximum tolerated dose (MTD) of SGN-CD123A Secondary Objectives Determine anticancer activity Assess Pharmacokinetics (PK) of SGN-CD123A Assess immunogenicity of SGN-CD123A Assess CD123 expression-response relationship Additional Assess biomarker of biological activity, and resistance and predictive biomarkers of response Assess Minimal Residual disease (MRD)
IRB Review and Approval Date: 01/19/2017
Recruitment Status: Open
Projected Accrual: 102
1) Relapsed/refractory acute myeloid leukemia.
2) Age >/= 18 and <75 years.
3) Patients who have received either 2 or 3 previous regimens to treat active disease. Post-remission treatments, intrathecal chemotherapy and radiotherapy are not considered previous regimens. Treatment regimens for myelodysplastic syndrome (MDS) preceding AML will not be counted as a previous regimen.
4) Patients may be eligible after only 1 previous regimen to treat active disease if at least one of the following apply: Age >/= 60 years (but <75 years) Primary resistant AML (defined as failure to achieve CR after 1 to 2 cycles of induction therapy) First complete remission (CR) duration <6 months Adverse-risk cytogenetics per Medical Research Council classification Secondary AML (prior history of MDS or therapy-related) FLT3-ITD mutation
5) Part A: CD123-detectable disease, as determined by central laboratory assessment. Detectable CD123 expression is defined as any signal above the lower limit of detection of the flow cytometric assay. CD123-detectability determined on bone marrow sample preferably; in cases when bone marrow result is not interpretable or the sample is acellular, CD123-detectability in blood is acceptable. Part B: CD123-detectable disease in at least the initial 20 patients, as determined by central laboratory assessment. Detectable CD123 expression is defined as any signal above the lower limit of detection of the flow cytometric assay. CD123-detectability determined on bone marrow sample preferably; in cases when bone marrow result is not interpretable or the sample is acellular, CD123-detectability in blood is acceptable.
6) An ECOG Performance Status score 0 or 1.
7) The following baseline laboratory data: serum bilirubin </= 1.5 × upper limit of normal (ULN) or </=3 × ULN for patients with Gilbert’s disease creatinine clearance >/+ 60 mL/min alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </=3 × ULN
8) Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (ß-hCG) pregnancy test result within 7 days prior to the first dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral oophorectomy or hysterectomy.
9) Females of childbearing potential and males who have partners of childbearing potential must agree to use 2 effective forms of contraception during the study and for 6 months following the last dose of study drug.
10) Patients must provide written informed consent.
1) Cerebral/meningeal disease related to the underlying malignancy.
Patients with a history of cerebral/meningeal disease related to the
underlying malignancy are allowed if prior central nervous system
disease has been definitively treated.
2) Patients with acute promyelocytic leukemia (APL).
3) Any uncontrolled active Grade 3 or higher (per the National Cancer Institute’s Common Terminology Criteria for Adverse Events [NCI CTCAE], Version 4.03) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of SGN-CD123A. Routine antimicrobial prophylaxis is permitted.
4) Patients with a history of clinically significant pulmonary fibrosis or documented diffusing capacity of the lung for carbon monoxide (DLCO) <50% of predicted.
5) Positive for hepatitis B by surface antigen expression. Active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months).
6) Known seropositivity or active infection by human immunodeficiency virus (HIV).
7) Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association (NYHA) Class III-IV (see Appendix C) within 6 months prior to their first dose of SGN-CD123A.
8) History of myeloproliferative neoplasm (MPN).
9) Prior hematopoietic stem cell transplant.
10) Anti-leukemia chemotherapy or any experimental therapy within 4 weeks of starting study treatment. Hydroxyurea or 6-mercaptopurine used for cytoreduction may be given up to 24 hours prior to treatment.
11) Females who are pregnant or breastfeeding.
12) Known hypersensitivity to any excipient contained in the drug formulation of SGN-CD123A.
13) Patients with a history of liver cirrhosis and /or active alcohol abuse.
14) Patients with prior use of SGN-CD33A and/or any CD33-targeted ADC.
15) Patients who are on supplemental oxygen or who have resting oxygen saturation of <90% on room air.
Information and next steps
Malignant neoplasms stated as primary lymphoid haematopoietic
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