Clinical Trials /

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

NCT02730312

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • B-Cell Acute Lymphoblastic Leukemia
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PH 1 Study to Evaluate Safety and Tolerability of XmAb14045 in Patients With CD123-expressing Hematologic Malignancies
  • 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 IDs

  • ORG STUDY ID: XmAb14045-01
  • NCT ID: NCT02730312

Conditions

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

Interventions

DrugSynonymsArms
XmAb14045XmAb14045

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
XmAb14045ExperimentalBiological/Vaccine: XmAb14045 Administered IV weekly up to 8 weeks
  • XmAb14045

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety as determined by the number of participants with treatment-related adverse events
Time Frame:Baseline Day 1 through Day 56
Safety Issue:
Description:Treatment-related adverse events as assessed by CTCAE v4.03

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Xencor, Inc.

Trial Keywords

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

Last Updated

November 27, 2019