A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Acute Myeloid Leukemia (AML)

NCT02610062 | Terminated Phase 1 FDA Drug

• 1 other identifier: AGS67E-15-2
• Study Type: interventional
• Target: 23
• Locations: 2 countries
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of AGS67E in subjects with acute myeloid leukemia (AML) and determine a safe dose for future development. In addition, this study will assess the pharmacokinetics (PK), the immunogenicity, and the anti-leukemic activity of AGS67E.

Conditions

Acute Myeloid Leukemia

Keywords

AML; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Incidence and nature of adverse events

  Up to 24 months

Secondary Outcomes (20)

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE) in dose escalation part: Concentration at the end of infusion (CEOI)

  Escalation Q3 weeks dosing: up to Day 15 for Cycle 1, Day 8 for Cycle 2, predose in subsequent cycles up to an average of 12 months. Escalation weekly dosing: up to Day 22 for Cycles 1, 2 and predose in subsequent cycles up to an average of 12 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE) in dose expansion part: Concentration at the end of infusion (CEOI)

  Expansion Q3 weeks dosing: up to Day 8 for Cycle 1, Day 3 for Cycle 2, predose in subsequent cycles up to an average of 12 months. Expansion weekly dosing: up to Day 22 for Cycles 1, 2 and predose in subsequent cycles up to an average of 12 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE) in dose escalation part: Maximum observed concentration (Cmax)

  Escalation Q3 weeks dosing: up to Day 15 for Cycle 1, Day 8 for Cycle 2, predose in subsequent cycles up to an average of 12 months. Escalation weekly dosing: up to Day 22 for Cycles 1, 2 and predose in subsequent cycles up to an average of 12 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE) in dose expansion part: Maximum observed concentration (Cmax)

  Expansion Q3 weeks dosing: up to Day 8 for Cycle 1, Day 3 for Cycle 2, predose in subsequent cycles up to an average of 12 months. Expansion weekly dosing: up to Day 22 for Cycles 1, 2 and predose in subsequent cycles up to an average of 12 months

• Pharmacokinetic parameter for Monomethyl Auristatin E (MMAE) in dose escalation part: Time to maximum concentration (Tmax)

  Escalation Q3 weeks dosing: up to Day 15 for Cycle 1, Day 8 for Cycle 2, predose in subsequent cycles up to an average of 12 months. Escalation weekly dosing: up to Day 22 for Cycles 1, 2 and predose in subsequent cycles up to an average of 12 months

Study Arms (5)

AGS67E 1.2 mg/kg Schedule 1

EXPERIMENTAL

Participants will receive 1.2 mg/kg of AGS67E as an intravenous infusion once every three weeks (Q3).

Drug: AGS67E

AGS67E 1.8 mg/kg Schedule 1

EXPERIMENTAL

Participants will receive 1.8 mg/kg of AGS67E as an intravenous infusion once every three weeks.

Drug: AGS67E

AGS67E 2.4 mg/kg Schedule 1

EXPERIMENTAL

Participants will receive 2.4 mg/kg of AGS67E as an intravenous infusion once every three weeks.

Drug: AGS67E

AGS67E 0.6 mg/kg Schedule 2

EXPERIMENTAL

Participants will receive 0.6 mg/kg of AGS67E once weekly for three weeks.

Drug: AGS67E

AGS67E 0.9 mg/kg Schedule 2

EXPERIMENTAL

Participants will receive 0.9 mg/kg of AGS67E once weekly for three weeks.

Drug: AGS67E

Interventions

AGS67E DRUG

Intravenous (IV) infusion

AGS67E 0.6 mg/kg Schedule 2; AGS67E 0.9 mg/kg Schedule 2; AGS67E 1.2 mg/kg Schedule 1; AGS67E 1.8 mg/kg Schedule 1; AGS67E 2.4 mg/kg Schedule 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has morphologically documented primary or secondary AML by the World Health Organization (WHO) criteria (2008) and fulfills one of the following:
• Refractory to at least 1 cycle of induction chemotherapy
• Relapsed after achieving remission with a prior therapy
• Patients with untreated AML who are either unwilling or unable to undergo high-dose induction/consolidation intensive chemotherapy
• Circulating blasts \< 20,000 (cytoreduction with hydroxyurea is allowed)
• Eastern Cooperative Oncology Group performance score (ECOG) ≤ 2
• Subject has adequate renal function: serum creatinine ≤ 2.0 mg/dL and estimated creatinine clearance of ≥ 30 mL/min by the Cockcroft-Gault equation
• Subject has a total bilirubin ≤ 1.5 x upper limit of normal (ULN), albumin ≥ 2.5 g/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
• Negative pregnancy test in women of child bearing potential
• Sexually active fertile subjects, and their partners, must agree to use medically accepted double-barrier methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the study and at least 6 weeks after termination of study therapy

You may not qualify if:

• Subject has a diagnosis of acute promyelocytic leukemia
• Subject has preexisting sensory or motor neuropathy Grade ≥ 2 at baseline
• Subject has received small molecule therapy, radiotherapy, immunotherapy, monoclonal antibodies, investigational drug, or chemotherapy within 14 days before first dose of study drug, with the exception of hydroxyurea
• P-gp inducers/inhibitors or strong CYP3A inhibitors within 14 days before the first dose of drug, with the exception of the antibiotics/ antifungals used as prophylaxis and/or supportive care
• Any Grade ≥ 2 persistent non-hematological toxicity related to allotransplant
• Graft-Versus-Host Disease (GVHD) therapy within 6 weeks before the first dose of study drug; low dose steroids (≤ 10mg) allowed
• Subject has known current central nervous system (CNS) disease
• Active angina or Class III or IV Congestive Heart Failure (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 6 months of the first dose of study drug, including myocardial infarction, unstable angina, Grade 2 or greater peripheral vascular disease, congestive heart failure, uncontrolled hypertension, or arrhythmias not controlled by medication
• Subject has clinical evidence of Disseminated Intravascular Coagulation (DIC)
• Subject has known positivity for human immunodeficiency virus (HIV)
• Subject has know positivity for Hepatitis B surface antigen test or Hepatitis C Antibody
• Subject has an uncontrolled active infection requiring treatment and fever 38.3°C or higher 48 hours before the first dose of study drug. Controlled infections (i.e. 3 negative cultures completing antibiotics and/or stable fungal infection in therapy are allowed provided the subject has a temperature of \<38.3°C within 48 hours of the first dose of study drug
• Subject has known sensitivity to any of the components of the investigational product AGS67E:
• AGS67E
• L-Histidine

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (4)

Site US0006

Duarte, California, 91010, United States

Location

Site US0004

New York, New York, 10016, United States

Location

Site US0001

Houston, Texas, 77030, United States

Location

Site CA0010

Toronto, Ontario, M5G 2M9, Canada

Location

Related Links

• Link to results on ACSR website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

AGS67E

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Associate Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2015
• First Posted: November 20, 2015
• Study Start: March 29, 2016
• Primary Completion: September 22, 2017
• Study Completion: November 21, 2017
• Last Updated: November 1, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); CA (1)