A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Escalating Doses of AGS67E Given as Monotherapy in Subjects With Refractory or Relapsed Lymphoid Malignancies

NCT02175433 | Completed Phase 1

• 1 other identifier: AGS67E-14-1
• Study Type: interventional
• Target: 71
• Locations: 2 countries
• Sites: 5

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of AGS67E both without and with myeloid growth factor (GF) in subjects with refractory or relapsed lymphoid malignancies. Immunogenicity and anticancer activity of AGS67E will also be assessed.

Conditions

Relapsed Lymphoid Malignancy; Refractory Lymphoid Malignancy

Keywords

Refractory or relapsed chronic lymphocytic leukemia (CLL) prolymphocytic leukemia (PLL); Relapsed lymphoid malignancy; Refractory lymphoid malignancy; Pharmacokinetics of AGS67E; hairy cell leukemia (HCL); AGS67C; non-Hodgkin lymphoma (NHL); AGS67E

Outcome Measures

Primary Outcomes (8)

• Incidence and nature of adverse events

  up to 34 months

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

  Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months

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

  Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months

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

  Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-21)

  Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2)

  Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL)

  Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months

• Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss)

  Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months

Secondary Outcomes (3)

• Incidence of Anti-Drug Antibody (ADA) formation to the fully human monoclonal antibody (AGS67C) and antibody-drug conjugate (AGS67E)

  Up to 34 months

• Incidence of tumor response

  Up to 34 months

• Objective response rate (ORR)

  Up to 34 months

Study Arms (11)

Dose Escalation of AGS67E 0.05 mg/kg Without GF

EXPERIMENTAL

Participants will receive 0.05 milligram per kilogram (mg/kg) AGS67E without growth factor (GF) by intravenous infusion once every three weeks.

Drug: AGS67E

Dose Escalation of AGS67E 0.1 mg/kg Without GF

EXPERIMENTAL

Participants will receive 0.1 mg/kg AGS67E without GF by intravenous infusion once every three weeks.

Drug: AGS67E

Dose Escalation of AGS67E 0.3 mg/kg Without GF

EXPERIMENTAL

Participants will receive 0.3 mg/kg AGS67E without GF by intravenous infusion once every three weeks.

Drug: AGS67E

Dose Escalation of AGS67E 0.6 mg/kg Without GF

EXPERIMENTAL

Participants will receive 0.6 mg/kg AGS67E without GF by intravenous infusion once every three weeks.

Drug: AGS67E

Dose Escalation of AGS67E 0.9 mg/kg Without GF

EXPERIMENTAL

Participants will receive 0.9 mg/kg AGS67E without GF by intravenous infusion once every three weeks.

Drug: AGS67E

Dose Escalation of AGS67E 1.2 mg/kg Without GF

EXPERIMENTAL

Participants will receive 1.2 mg/kg AGS67E without GF by intravenous infusion once every three weeks.

Drug: AGS67E

Dose Expansion of AGS67E 0.9 mg/kg Without GF

EXPERIMENTAL

Participants will receive 0.9 mg/kg AGS67E without GF by intravenous infusion once every three weeks.

Drug: AGS67E

Dose Escalation of AGS67E 1.2 mg/kg With GF

EXPERIMENTAL

Participants will receive 1.2 mg/kg AGS67E with GF by intravenous infusion once every three weeks.

Drug: AGS67E

Dose Escalation of AGS67E 1.5 mg/kg With GF

EXPERIMENTAL

Participants will receive 1.5 mg/kg AGS67E with GF by intravenous infusion once every three weeks.

Drug: AGS67E

Dose Escalation of AGS67E 1.8 mg/kg With GF

EXPERIMENTAL

Participants will receive 1.8 mg/kg AGS67E with GF by intravenous infusion once every three weeks.

Drug: AGS67E

Dose Expansion of AGS67E 1.5 mg/kg With GF

EXPERIMENTAL

Participants will receive 1.5 mg/kg AGS67E with GF by intravenous infusion once every three weeks.

Drug: AGS67E

Interventions

AGS67E DRUG

intravenous (IV) infusion

Dose Escalation of AGS67E 0.05 mg/kg Without GF; Dose Escalation of AGS67E 0.1 mg/kg Without GF; Dose Escalation of AGS67E 0.3 mg/kg Without GF; Dose Escalation of AGS67E 0.6 mg/kg Without GF; Dose Escalation of AGS67E 0.9 mg/kg Without GF; Dose Escalation of AGS67E 1.2 mg/kg With GF; Dose Escalation of AGS67E 1.2 mg/kg Without GF; Dose Escalation of AGS67E 1.5 mg/kg With GF; Dose Escalation of AGS67E 1.8 mg/kg With GF; Dose Expansion of AGS67E 0.9 mg/kg Without GF; Dose Expansion of AGS67E 1.5 mg/kg With GF

Eligibility Criteria

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

You may qualify if:

• Refractory or relapsed chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), hairy cell leukemia (HCL) or non-Hodgkin lymphoma (NHL) (including those of T cell origin)
• Eastern Cooperative Oncology Group performance score (ECOG) ≤ 2
• Negative pregnancy test (women of childbearing potential)
• Hematologic function, as follows (no platelet transfusion within 2 weeks and no RBC transfusion within 4 days before the first dose of study drug)
• Absolute neutrophil count (ANC) ≥ 1,000/μL
• Platelets ≥ 75,000/μL
• Hemoglobin ≥ 8 g/dL (may be transfused ≥ 5 days)
• Renal function: serum creatinine ≤ 2.0 mg/dL and estimated creatinine clearance of ≥ 45 mL/min by the Cockcroft-Gault equation
• Direct bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Serum albumin ≥ 2.5 g/dL
• Aspartate aminotransferase (AST) ≤ 1.5 x ULN unless there is hepatic involvement, then 3 x ULN
• Alanine aminotransferase (ALT) ≤ 1.5 x ULN unless there is hepatic involvement, then 3 x ULN
• 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:

• Preexisting sensory and/or motor neuropathy Grade ≥ 2
• Small molecule therapy, radiotherapy, immunotherapy, monoclonal antibodies, or chemotherapy within 2 weeks before first dose of study drug
• Radioimmunotherapy within 4 weeks before first dose of study drug
• Use of any investigational drug (including marketed drugs not approved for this indication) within 14 days prior to the first dose of study drug
• Any P-gp inducers/inhibitors or strong CYP3A inhibitors within 2 weeks before the first dose of study drug (See Appendix F for list of excluded drugs)
• Anti Graft-Versus-Host Disease (GVHD) therapy within 12 weeks before the first dose of study drug
• Platelet transfusion within 2 weeks and RBC transfusion within 4 days before the first dose of study drug
• Known central nervous system (CNS) disease
• History of other primary malignancy (including myeloid malignancy, e.g., myelodysplastic syndrome), unless
• Curatively resected nonmelanomatous skin cancer
• Other malignancy curatively treated with no known active disease present and no systemic treatment administered for 3 years before the first dose of study drug
• Active angina or Class III or IV Congestive Heart Failure (CHF) (New York Heart Association CHF Functional Classification System) or clinically significant cardiac disease within 12 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 outpatient medication
• Women who are pregnant or lactating
• Known HIV positive or AIDS
• Positive Hepatitis B surface antigen test

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (5)

Site US0006

Duarte, California, 91010, United States

Location

Site US0002

Stanford, California, 94305, United States

Location

Site US0004

Fairway, Kansas, 66205, United States

Location

Site US0001

New York, New York, 10019, United States

Location

Site CA0005

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Related Links

• Link to results on the Astellas Clinical Study Results website.

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic; Leukemia, Hairy Cell; Lymphoma, Non-Hodgkin

Interventions

AGS67E

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma

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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2014
• First Posted: June 26, 2014
• Study Start: October 14, 2014
• Primary Completion: October 29, 2019
• Study Completion: October 29, 2019
• Last Updated: November 1, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

US (4); CA (1)