PH 1 Study to Evaluate Safety and Tolerability of XmAb14045 in Patients With CD123-expressing Hematologic Malignancies

• ClinicalTrials.gov Identifier: NCT02730312
• Recruitment Status: Completed
• First Posted: April 6, 2016
• Last Update Posted: March 8, 2022
• Sponsor: Xencor, Inc.
• Collaborator: ICON Clinical Research
• Information provided by (Responsible Party): Xencor, Inc.

Study Description

Brief Summary:

The purpose of this study is to determine the safety and tolerability of weekly intravenous (IV) administration of XmAb14045 and to determine the maximally tolerated dose (MTD) after the first dose, and then to determine the MTD after second and subsequent infusions.

Condition or disease	Intervention/treatment	Phase
Acute Myelogenous Leukemia; B-cell Acute Lymphoblastic Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Chronic Myeloid Leukemia, Blast Crisis	Biological: XmAb14045	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Multiple Dose Study to Evaluate the Safety and Tolerability of XmAb®14045 in Patients With CD123-Expressing Hematologic Malignancies
• Actual Study Start Date: August 2016
• Actual Primary Completion Date: September 2021
• Actual Study Completion Date: September 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: XmAb14045; Biological/Vaccine: XmAb14045 Administered IV weekly up to 8 weeks	Biological: XmAb14045; Administered IV weekly up to 8 weeks, with or without step-up dosing

Outcome Measures

Primary Outcome Measures :

1. Safety as determined by the number of participants with treatment-related adverse events [ Time Frame: Baseline Day 1 through Day 56 ]
   Treatment-related adverse events as assessed by CTCAE v4.03
2. Identify maximum tolerated (MTD) and/or recommended dose (RD) and schedule for XmAb14045 dosing [ Time Frame: Baseline Day 1 through Day 56 ]
   Identify maximum tolerated (MTD) and/or recommended dose (RD) and schedule for XmAb14045 dosing

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of 1 of the following diseases:

  • Primary or secondary AML (including erythroleukemia and eosinophilic leukemia, but excluding acute promyelocytic leukemia)
  • B-cell ALL
  • BPDCN
  • CML in blast phase, resistant or intolerant to tyrosine kinase inhibitor therapy
• Patients with relapsed or refractory disease with no available standard therapy
• ECOG performance status 0-2
• Not a candidate for, or refusing treatment with hematopoietic stem cell transplantation
• Fertile patients must agree to use effective contraception during and for 4 weeks after the last dose of XmAb14045
• Male patients must agree to use highly effective contraception, and refrain from donating sperm during the treatment period and for at least 4 weeks after the last dose of XmAb14045
• Able and willing to complete the entire study

Exclusion Criteria:

• Systemic antineoplastic therapy (including cytotoxic chemotherapy and toxin immunoconjugates, but excluding hydroxyurea), unconjugated antibody therapy, or radiotherapy within 2 weeks of the first dose of study treatment, or small molecule kinase inhibitors within 6 elimination half-lives of the first dose of study treatment.
• Prior therapy with CD123- or IL-3R-directed immunotherapies, including monospecific and bsAbs, immunoconjugates, or chimeric antigen receptor- modified T-cell therapy
• Failure to recover from Grade 3 or 4 toxicity from previous treatment (unrelated to malignant bone marrow involvement)
• Known uncontrolled central nervous system involvement by malignant disease
• Absolute blast count ≥10,000/mm3 or symptoms of leukostasis
• Diagnosis of promyelocytic leukemia
• Aspartate aminotransferase or alanine aminotransferase at screening >3.0 x upper limit of normal (ULN) unless considered due to leukemic organ involvement
• Bilirubin >1.5 x ULN, unless prior diagnosis and documentation of leukemic organ involvement, ongoing hemolysis, or Gilbert's syndrome
• Serum creatinine >2.0 x ULN, or estimated creatinine clearance <40mL/min
• Active heart failure or New York Heart Association Class III or IV or Objective Assessment C or D
• History or evidence of a clinically unstable/uncontrollable disorder, condition or disease other than primary malignancy, that in the opinion of the Investigator would pose a risk to the patient safety or interfere with the study evaluation, procedures, or completion
• Evidence of any active, uncontrolled bacterial, viral, parasitic, or systemic fungal infections within 1 week of first dose of study drug
• Positive test for human immunodeficiency virus (HIV) -I or -II antibodies, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus (HCV) antibody (unless HCV viral load test by PCR is negative). HBcAb positivity will be allowed if one or more of the following is true: a) HBsAb is present; b) hepatitis B DNA testing is negative and the patient is receiving hepatitis B reactivation prophylaxis with entecavir, tenofovir, or lamivudine
• Patient is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the End of Study visit
• Patients with substance abuse or other medical or psychiatric conditions that, in the opinion of the Investigator, would confound study interpretation or affect the patient's ability to tolerate or complete the study

Contacts and Locations

Locations

United States, Florida

Mayo Clinic Jacksonville

Jacksonville, Florida, United States, 32224

United States, Georgia

Emory University Hospital Midtown

Atlanta, Georgia, United States, 30308

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States, 30322

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, United States, 30342

Northside Hospital

Atlanta, Georgia, United States, 30342

United States, Illinois

The University of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, Ohio

Wexner Medical Center at The Ohio State University

Columbus, Ohio, United States, 43210

United States, Texas

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Washington

Swedish Cancer Institute

Seattle, Washington, United States, 98104

Sponsors and Collaborators

Xencor, Inc.

ICON Clinical Research

Investigators

• Study Director: Raman Garcha, MD; Xencor, Inc.

More Information

• Responsible Party: Xencor, Inc.
• ClinicalTrials.gov Identifier: NCT02730312
• Other Study ID Numbers: XmAb14045-01
• First Posted: April 6, 2016
• Last Update Posted: March 8, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Xencor, Inc.:

AML; B-ALL; BPDCN; CML; Blast Crisis

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid; Hematologic Neoplasms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Blast Crisis; Neoplasms by Histologic Type; Neoplasms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Hematologic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes