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

Acute Myelogenous Leukemia Clinical Trial

Official title:

A Phase 1 Multiple Dose Study to Evaluate the Safety and Tolerability of XmAb®14045 in Patients With CD123-Expressing Hematologic Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02730312
• Other study ID #: XmAb14045-01
• Status: Completed
• Phase: Phase 1
• Start date: August 2016
• Est. completion date: September 2021

Study information

• Verified date: March 2022
• Source: Xencor, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: September 2021
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• B-cell Acute Lymphoblastic Leukemia
• Blast Crisis
• Blastic Plasmacytoid Dendritic Cell Neoplasm
• Chronic Myeloid Leukemia, Blast Crisis
• Hematologic Neoplasms
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• XmAb14045
Administered IV weekly up to 8 weeks, with or without step-up dosing

Locations

Country	Name	City	State
United States	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Northside Hospital	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	Wexner Medical Center at The Ohio State University	Columbus	Ohio
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic Jacksonville	Jacksonville	Florida
United States	Swedish Cancer Institute	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Xencor, Inc.	ICON Clinical Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as determined by the number of participants with treatment-related adverse events	Treatment-related adverse events as assessed by CTCAE v4.03	Baseline Day 1 through Day 56
Primary	Identify maximum tolerated (MTD) and/or recommended dose (RD) and schedule for XmAb14045 dosing	Identify maximum tolerated (MTD) and/or recommended dose (RD) and schedule for XmAb14045 dosing	Baseline Day 1 through Day 56