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

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ClinicalTrials.gov Identifier: NCT01211691
Recruitment Status : Suspended (KaloBios to Wind Down Operations)
First Posted : September 29, 2010
Last Update Posted : November 17, 2015
Sponsor:
Information provided by (Responsible Party):
Humanigen, Inc.

Tracking Information
First Submitted Date  ICMJE September 24, 2010
First Posted Date  ICMJE September 29, 2010
Last Update Posted Date November 17, 2015
Study Start Date  ICMJE September 2010
Estimated Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 4, 2013)
  • Phase 1: Determine a possible maximum tolerated dose (MTD) [ Time Frame: Once weekly for the first three weeks of study treatment ]
  • Phase 2: To characterize preliminary clinical activity based on the International Working Group (IWG) criteria specific to the hematologic malignancy [ Time Frame: Evaluations at designated timepoints ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 28, 2010)
Determine a possible maximum tolerated dose (MTD) [ Time Frame: Once weekly for the first three weeks of study treatment ]
Determination of a possible MTD as assessed by the number of subjects experiencing treatment emergent adverse events considered dose limiting in nature
Change History Complete list of historical versions of study NCT01211691 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2013)
  • Phase 1: Examine clinical activity [ Time Frame: Evaluations at designated timepoints ]
  • Phase 1/2: Safety and Tolerability [ Time Frame: Duration of study participation ]
  • Phase 1/2: Pharmacokinetic profile [ Time Frame: Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles ]
  • Phase 1/2: Assess immunogenicity [ Time Frame: Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2010)
  • Safety and Tolerability [ Time Frame: Assessed through weekly subject evaluations for the entire duration of study participation (up to 1 year) ]
    Number of subjects with adverse events and laboratory abnormalities as a measure of safety and tolerability
  • Pharmacokinetic profile [ Time Frame: Prior to study drug administration (ADMIN) & then at end of study drug ADMIN & 1, 3, 6 hrs post study drug ADMIN. Subsequent doses: Day 8 & Day 15 of Dosing Cycle 1 & Day 1 of Dosing Cycles 2, 3, 6, 9, 12 & 15 [Dosing Cycles each @ 3wks] ]
    The amount of KB004 in subject serum over time as a measure of its pharmacokinetic profile
  • Pharmacodynamic effects on relevant tumor cell subpopulations [ Time Frame: Baseline and Day 1 of Dosing Cycles 2 (optional), 3, 6, 9, 12, and 15 ]
    Change from baseline in the amount of EphA3-expressing tumor cells by subpopulation in subject blood or bone marrow
  • Assess immunogenicity [ Time Frame: Baseline, Day 8, and Day 15 of Dosing Cycle 1, and Day 1 of Dosing Cycles 2, 3, 6, 9, 12, and 15 ]
    The development of anti-KB004 antibodies in subject blood as a measure of immunogenicity
  • Examine clinical activity [ Time Frame: Baseline and Day 1 of Dosing Cycles 2 (optional), 3, 6, 9, 12, and 15 ]
    The number of subject with reduced hematologic malignancy signs and symptoms as a measure of clinical activity
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of KB004 in Subjects With Hematologic Malignancies (Myelodysplastic Syndrome, MDS, Myelofibrosis, MF)
Official Title  ICMJE Study of the Anti-EphA3 Monoclonal Antibody KB004 in Subjects With EphA3-Expressing Hematologic Malignancies
Brief Summary 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Myelodysplastic Syndrome (MDS)
  • Myelofibrosis (MF)
Intervention  ICMJE Drug: KB004, Monoclonal Antibody
Study Arms  ICMJE
  • Experimental: Phase 1 dose levels: KB004

    IV 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)

    Intervention: Drug: KB004, Monoclonal Antibody
  • Experimental: Phase 2 dose levels: KB004

    IV infusion 1x Weekly for a 21 day dosing cycle

    Subjects will be assigned to the recommended Phase 2 dose of 250 mg

    Intervention: Drug: KB004, Monoclonal Antibody
Publications * Swords RT, Greenberg PL, Wei AH, Durrant S, Advani AS, Hertzberg MS, Jonas BA, Lewis ID, Rivera G, Gratzinger D, Fan AC, Felsher DW, Cortes JE, Watts JM, Yarranton GT, Walling JM, Lancet JE. KB004, a first in class monoclonal antibody targeting the receptor tyrosine kinase EphA3, in patients with advanced hematologic malignancies: Results from a phase 1 study. Leuk Res. 2016 Nov;50:123-131. doi: 10.1016/j.leukres.2016.09.012. Epub 2016 Sep 28. Erratum in: Leuk Res. 2017 Aug;59:65.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: April 7, 2015)
120
Original Estimated Enrollment  ICMJE
 (submitted: September 28, 2010)
39
Estimated Study Completion Date  ICMJE December 2016
Estimated Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01211691
Other Study ID Numbers  ICMJE KB004-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Humanigen, Inc.
Study Sponsor  ICMJE Humanigen, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Morgan Lam Humanigen, Inc.
PRS Account Humanigen, Inc.
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP