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

NCT02730312 | Completed Phase 1 FDA Drug

• 1 other identifier: XmAb14045-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 9

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.

Conditions

Acute Myelogenous Leukemia; B-cell Acute Lymphoblastic Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Chronic Myeloid Leukemia, Blast Crisis

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Study Arms (1)

XmAb14045

EXPERIMENTAL

Biological/Vaccine: XmAb14045 Administered IV weekly up to 8 weeks

Biological: XmAb14045

Interventions

XmAb14045 BIOLOGICAL

Administered IV weekly up to 8 weeks, with or without step-up dosing

XmAb14045

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Xencor, Inc.: lead
• ICON Clinical Research: collaborator

Study Sites (9)

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Wexner Medical Center at The Ohio State University

Columbus, Ohio, 43210, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• Ravandi F, Bashey A, Foran J, Stock W, Mawad R, Short N, Yilmaz M, Kantarjian H, Odenike O, Patel A, Garcha R, Ainsworth WB, Clynes R, Kanodia J, Ding Y, Li H, Kye S, Mims A. Phase 1 study of vibecotamab identifies an optimized dose for treatment of relapsed/refractory acute myeloid leukemia. Blood Adv. 2023 Nov 14;7(21):6492-6505. doi: 10.1182/bloodadvances.2023010956.

  PMID: 37647601 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Burkitt Lymphoma; Blastic Plasmacytoid Dendritic Cell Neoplasm; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Blast Crisis

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Histiocytic Disorders, Malignant; Hematologic Neoplasms; Neoplasms by Site; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

Study Officials

• Raman Garcha, MD

  Xencor, Inc.

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 31, 2016
• First Posted: April 6, 2016
• Study Start: August 1, 2016
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2021
• Last Updated: March 8, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)