Clinical Trials /

Study of KB004 in Subjects With Hematologic Malignancies (Myelodysplastic Syndrome, MDS, Myelofibrosis, MF)

NCT01211691

Description:

This is a global, multicenter, open-label, repeat-dose, Phase 1/2 study consisting of a Dose Escalation Phase (Phase 1) and a Cohort Expansion Phase (Phase 2). In both phases, KB004 will be administered by IV infusion once weekly as part of a 21-day dosing cycle.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Suspended

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of KB004 in Subjects With Hematologic Malignancies (Myelodysplastic Syndrome, MDS, Myelofibrosis, MF)
  • Official Title: Study of the Anti-EphA3 Monoclonal Antibody KB004 in Subjects With EphA3-Expressing Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: KB004-01
  • NCT ID: NCT01211691

Conditions

  • Myelodysplastic Syndrome (MDS)
  • Myelofibrosis (MF)

Interventions

DrugSynonymsArms
KB004, Monoclonal AntibodyPhase 1 dose levels: KB004

Purpose

This is a global, multicenter, open-label, repeat-dose, Phase 1/2 study consisting of a Dose Escalation Phase (Phase 1) and a Cohort Expansion Phase (Phase 2). In both phases, KB004 will be administered by IV infusion once weekly as part of a 21-day dosing cycle.

Detailed Description

      The purpose of Phase 1 is to determine a maximum tolerated dose (MTD) for KB004 when
      administered to subjects with hematologic malignancies who meet the entry criteria. Phase 1
      has completed enrollment July of 2014, the recommended Phase 2 dose is 250 mg. AML 20 mg
      Cohort completed enrollment Dec 2014.

      The purpose of Phase 2 is to characterize preliminary clinical activity. The Phase 2 portion
      of the study consists of two parts:

        -  Part A: Subjects with AML or MDS who meet the entry criteria

        -  Part B: Subjects with MF who meet the entry criteria
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 dose levels: KB004ExperimentalIV infusion 1x Weekly for a 21 day dosing cycle Subjects with heme malignancies will be assigned to one of 11 planned KB004 (dose levels (20mg, 40mg, 70mg, 100mg, 140mg, 190mg, 250mg, 330mg)
  • KB004, Monoclonal Antibody
Phase 2 dose levels: KB004ExperimentalIV infusion 1x Weekly for a 21 day dosing cycle Subjects will be assigned to the recommended Phase 2 dose of 250 mg
  • KB004, Monoclonal Antibody

Eligibility Criteria

        Key Inclusion Criteria (Phase 1):

        - Confirmed hematologic malignancy, including Acute Myeloid Leukemia (AML), Chronic
        Lymphocytic Leukemia (CLL), Chronic Myelogenous Leukemia (CML), Acute Lymphocytic Leukemia
        (ALL), Myelodysplastic Syndrome (MDS), Multiple Myeloma (MM), Myelofibrosis (MF),
        Myeloproliferative Neoplasms (MPN) or MDS/MPN overlap diseases. (Once Phase 2 has started
        subjects with AML will be eligible for inclusion in the Phase 1 portion of the study only
        if their malignancy has been shown to have c-Cbl mutation, trisomy 3, trisomy 11, inv(16),
        or elevated FLT3. [Other AML and subjects with MDS will no longer be eligible for inclusion
        in the Phase 1 portion of the study]).

        Key Inclusion Criteria (Phase 2):

          -  Part A: AML or MDS patients with an acceptable level of EphA3 expression

          -  Part B: MF patients with an acceptable level of EphA3 expression

        Key Inclusion Criteria (Both Phases):

          -  Confirmed hematologic malignancy refractory to or progressed following standard
             treatments, or subjects not considered medically suitable to receive standard of care
             treatment or who refuse standard of care treatment

          -  Acceptable level of EphA3 expression

          -  Eastern Cooperative Oncology Group (ECOG) ≤1

          -  Acceptable laboratory results

        Key Exclusion Criteria (Both Phases):

          -  For subjects with AML, more than 2 prior therapies for AML (induction and
             consolidation with or without a hypomethylating agent given in a maintenance setting
             are considered 1 therapy)

          -  History of or current central nervous system (CNS) involvement that may increase risk
             of bleeding

          -  Recent major surgery

          -  Ongoing surgical or wound healing complications

          -  Active clinically significant bleeding

          -  Uncontrolled hypertension

          -  Significant intercurrent illness

          -  Known history of prolonged bleeding times or platelet dysfunction

          -  Active infection requiring IV antibiotics, IV antifungals, or IV antivirals within 2
             weeks prior to Cycle 1, Day 1
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Determine a possible maximum tolerated dose (MTD)
Time Frame:Once weekly for the first three weeks of study treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Phase 1: Examine clinical activity
Time Frame:Evaluations at designated timepoints
Safety Issue:
Description:
Measure:Phase 1/2: Safety and Tolerability
Time Frame:Duration of study participation
Safety Issue:
Description:
Measure:Phase 1/2: Pharmacokinetic profile
Time Frame:Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles
Safety Issue:
Description:
Measure:Phase 1/2: Assess immunogenicity
Time Frame:Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Suspended
Lead Sponsor:Humanigen, Inc.

Trial Keywords

  • Hematologic
  • Leukemia
  • Malignancies
  • Myeloproliferative Neoplasms

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