Back to resultsStudy of KB004 in Subjects With Hematologic Malignancies (Myelodysplastic Syndrome, MDS, Myelofibrosis, MF)
Primary Purpose
Myelodysplastic Syndrome (MDS), Myelofibrosis (MF)
Status
Suspended
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
KB004, Monoclonal Antibody
Sponsored by
About this trial
This is an interventional treatment trial for Myelodysplastic Syndrome (MDS) focused on measuring Hematologic, Leukemia, Malignancies, Myeloproliferative Neoplasms
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Phase 1 dose levels: KB004
Phase 2 dose levels: KB004
Arm Description
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)
IV infusion 1x Weekly for a 21 day dosing cycle Subjects will be assigned to the recommended Phase 2 dose of 250 mg
Outcomes
Primary Outcome Measures
Phase 1: Determine a possible maximum tolerated dose (MTD)
Phase 2: To characterize preliminary clinical activity based on the International Working Group (IWG) criteria specific to the hematologic malignancy
Secondary Outcome Measures
Phase 1: Examine clinical activity
Phase 1/2: Safety and Tolerability
Phase 1/2: Pharmacokinetic profile
Phase 1/2: Assess immunogenicity
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01211691
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2015
Overall Recruitment Status
Suspended
Why Stopped
KaloBios to Wind Down Operations
Study Start Date
September 2010 (undefined)
Primary Completion Date
July 2016 (Anticipated)
Study Completion Date
December 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Humanigen, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome (MDS), Myelofibrosis (MF)
Keywords
Hematologic, Leukemia, Malignancies, Myeloproliferative Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 dose levels: KB004
Arm Type
Experimental
Arm Description
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)
Arm Title
Phase 2 dose levels: KB004
Arm Type
Experimental
Arm Description
IV infusion 1x Weekly for a 21 day dosing cycle
Subjects will be assigned to the recommended Phase 2 dose of 250 mg
Intervention Type
Drug
Intervention Name(s)
KB004, Monoclonal Antibody
Primary Outcome Measure Information:
Title
Phase 1: Determine a possible maximum tolerated dose (MTD)
Time Frame
Once weekly for the first three weeks of study treatment
Title
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
Secondary Outcome Measure Information:
Title
Phase 1: Examine clinical activity
Time Frame
Evaluations at designated timepoints
Title
Phase 1/2: Safety and Tolerability
Time Frame
Duration of study participation
Title
Phase 1/2: Pharmacokinetic profile
Time Frame
Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles
Title
Phase 1/2: Assess immunogenicity
Time Frame
Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morgan Lam
Organizational Affiliation
Humanigen, Inc.
Official's Role
Study Director
Facility Information:
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
City
Manhattan
State/Province
New York
ZIP/Postal Code
10029
Country
United States
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
City
Prahran
State/Province
Victoria
ZIP/Postal Code
3007
Country
Australia
12. IPD Sharing Statement
Citations:
PubMed Identifier
27736729
Citation
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.
Results Reference
derived
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Study of KB004 in Subjects With Hematologic Malignancies (Myelodysplastic Syndrome, MDS, Myelofibrosis, MF)
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