Study to Find a Safe and Effective Dose of SKI-G-801 in the Treatment of Patients With Acute Myeloid Leukemia (AML)

Study Overview
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Brief Summary
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This Phase I study is designed to assess the safety, tolerability, pharmacokinetics and anti-tumor effect of increasing doses of study drug SKI-G-801 in patients with relapsed or refractory Acute Myeloid Leukemia (AML) who are unresponsive to currently available therapies. Eligible participants will receive cycles of treatment involving IV infusion of SKI-G-801 daily for 14 days followed by 14 days off. Treatment cycles will be repeated until progressive disease or unacceptable toxicity.

Official Title
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A Phase 1 Dose Escalation Trial of SKI-G-801 in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: SKI-G-801


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent for participation, prior to completing any study-related procedures. Diagnosis of Acute Myeloid Leukemia (AML) Patients must have been off previous antileukemia therapy for at least 2 weeks or 5 half-lives, whichever is longer if the immediate prior regimen included only weekly chemotherapy; or 4 weeks or 5 half-lives, whichever is longer, from any therapy with therapeutic biologics and from any type of investigational therapy. Daily hydroxyurea for up to 2 weeks to keep the absolute blast count below 50 x 10⁹/L will be allowed, but must be discontinued 24 hours prior to administration of study drug. Hydroxyurea will be permitted during the first cycle of treatment if necessary. At least one prior induction regimen (with or without consolidation) which may have included hematopoietic stem cell transplantation (HSCT). Have adequate liver function. Have adequate renal (kidney) function. Female patients must either be of non-childbearing potential, or, if of childbearing potential, have a negative urine pregnancy test at screening and agree not to try to become pregnant during the study and for 45 days after the final study drug administration. Women of childbearing potential, if heterosexually active, must agree to use 2 forms of highly effective birth control as determined by the protocol, starting at screening, throughout the study period and for 45 days after the final study drug administration. Female patients must agree not to breastfeed at screening, throughout the study period and for 45 days after the final study drug administration. Male patients with female spouse/partner of childbearing potential, must agree to use 2 forms of highly effective birth control as determined by the protocol, starting at screening, throughout the study period and for 45 days after the final study drug administration. Exclusion Criteria: Patient has a diagnosis of Acute Promyelocytic Leukemia (APL) or chronic myelogenous leukemia in blast crisis. If patient is post allogenic transplant and requires therapy for graft vs host disease (GVHD) within 14 days prior to date of screening. Requires treatment with concomitant drugs that prolong QT/QTc interval. Recent history of cardiac ischemic disease (acute myocardial infarction within 6 months; uncontrolled angina); severe uncontrolled ventricular arrhythmia; recent transient ischemic attack or stroke within 6 months of screening; poorly controlled hypertension (systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg). Patient has active, untreated central nervous system (CNS) disease. Other protocol defined inclusion/exclusion criteria could apply.

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: Dose Escalation Cohort<br>To identify the recommended phase 2 dose (RP2D) of SKI-G-801 in patients with relapsed or refractory AML (Acute Myeloid Leukemia) | Drug: SKI-G-801<br>* SKI-G-801 is administered as an IV infusion over 10 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recommended phase 2 dose (RP2D) | RP2D of SKI-G-801 determined using Neuenschwander's continual reassessment method (N-CRM) | From Cycle 1, Day 1 until disease progression, unacceptable toxicity, patient withdrawal from study, or judged not to be in patient's interest to continue in study, assessed up to 36 months | 
| Patients in complete remission or showing partial response (overall response rate [ORR]) | Number of patients showing composite complete remission (complete remission [CR], complete remission with incomplete platelet recovery [CRp], and complete remission with incomplete hematologic recovery [CRi]) of SKI-G-801 according to the Response Criteria in AML | Up to 30 days following last dose of study drug | 
| Patients in complete remission | Number of patients showing complete remission (CR) | Day 84 (± 3 days) | 
| Duration of remission | Number of days between a patient's first reported status of complete remission (CR) and the earlier of disease relapse or death from any cause | From date of first reported status of CR to the date of disease relapse or death (+ 1 day); or to date of last available disease status report for patients who do not relapse, assessed up to 36 months | 
| Duration of event free survival | Number of days between start of treatment to date of event | Day 1 to date of event (first documented treatment failure, relapse from CR or Cri [CR with incomplete hematologic recovery], or death due to any cause), assessed up to 36 months | 
| Time to treatment response (TTR) | Number of days between the start of treatment to the date of first subsequent disease status of complete remission (CR) | Day 1 to date of first subsequent disease status of CR (+ 1 day), assessed up to 36 months | 
| Dose limiting toxicity (DLT) Adverse Events (AEs) | Number of any DLT AEs within the first cycle of each patient's treatment with SKI-G-801 | Up to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) | Number, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] v4.03), seriousness and relatedness to treatment of treatment-emergent AEs | Up to 30 days following last dose of study drug | 
| Number of participants with clinical laboratory abnormalities |  | Up to 30 days following last dose of study drug | 
| Number of participants with overall safety profiles |  | Up to 30 days following last dose of study drug | 
| Number of participants with electrocardiogram (ECG) abnormalities |  | Up to 30 days following last dose of study drug |