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

Sponsor

Xencor, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02730312

Collaborator

ICON Clinical Research (Industry)

120

Enrollment

Locations

Arm

Actual Duration (Months)

13.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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

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 :

Aug 1, 2016

Actual Primary Completion Date :

Sep 1, 2021

Actual Study Completion Date :

Sep 1, 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

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
2	Emory University Hospital Midtown	Atlanta	Georgia	United States	30308
3	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
4	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia	United States	30342
5	Northside Hospital	Atlanta	Georgia	United States	30342
6	The University of Chicago Medical Center	Chicago	Illinois	United States	60637
7	Wexner Medical Center at The Ohio State University	Columbus	Ohio	United States	43210
8	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
9	Swedish Cancer Institute	Seattle	Washington	United States	98104