Myelodysplastic Syndrome (MDS)Phase 1/2NCT01211691
Study of KB004 in Subjects With Hematologic Malignancies (Myelodysplastic Syndrome, MDS, Myelofibrosis, MF)
A Phase 1/2 study testing KB004, Monoclonal Antibody in people with Myelodysplastic Syndrome (MDS) and Myelofibrosis (MF), run by Humanigen, Inc. at 9 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome (MDS), Myelofibrosis (MF)
- What is being tested?
- KB004, Monoclonal Antibody
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 9 sitesin 2 countries
- Study dates
- Sep 2010to Dec 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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]).
- Part A: AML or MDS patients with an acceptable level of EphA3 expression
- Part B: MF patients with an acceptable level of EphA3 expression
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States7 sites
Study site
Cleveland, Ohio, 44195
Study site
Houston, Texas, 77030
Study site
Manhattan, New York, 10029
Study site
Miami, Florida, 33136
Study site
Palo Alto, California, 94304
Study site
Sacramento, California, 95817
Study site
Tampa, Florida, 33612
Australia2 sites
Study site
Adelaide, South Australia, 5000
Study site
Prahran, Victoria, 3007
About this study
Official title: Study of the Anti-EphA3 Monoclonal Antibody KB004 in Subjects With EphA3-Expressing Hematologic Malignancies
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.
Read the 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
- Conditions
- Myelodysplastic Syndrome (MDS), Myelofibrosis (MF)
- Being tested
- KB004, Monoclonal Antibody
- Keywords
- Hematologic, Leukemia, Malignancies, Myeloproliferative Neoplasms
- Medical subject headings
- Myelodysplastic Syndromes, Primary Myelofibrosis, Leukemia, Neoplasms, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KB004, Monoclonal AntibodyDrug
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 dose levels: KB004 | Experimental | 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) Receives: Drug: KB004, Monoclonal Antibody |
| Phase 2 dose levels: KB004 | Experimental | IV infusion 1x Weekly for a 21 day dosing cycle
Subjects will be assigned to the recommended Phase 2 dose of 250 mg Receives: Drug: KB004, Monoclonal Antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Determine a possible maximum tolerated dose (MTD)
Measured: 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
Measured: Evaluations at designated timepoints
Secondary outcomes (4)
Phase 1: Examine clinical activity
Measured: Evaluations at designated timepoints
Phase 1/2: Safety and Tolerability
Measured: Duration of study participation
Phase 1/2: Pharmacokinetic profile
Measured: Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles
Phase 1/2: Assess immunogenicity
Measured: Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2010 (estimated)
- Study startSep 2010
- Primary completionJul 2016 (estimated)
- Study completionDec 2016 (estimated)
Why it stopped: KaloBios to Wind Down Operations
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myelodysplastic Syndrome (MDS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Humanigen, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Morgan Lam, Study director, Humanigen, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01211691
- Sponsor's protocol ID
- KB004-01
- Status last verified
- Nov 2015
- First submitted
- 24 Sep 2010
- Last updated
- 17 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 27736729
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Anti-EphA3 Monoclonal Antibody KB004 in Subjects With EphA3-Expressing Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT01211691
- Acronym / sponsor ID
- KB004-01
- Conditions
- Myelodysplastic Syndrome (MDS), Myelofibrosis (MF)
- Keywords
- Hematologic, Leukemia, Malignancies, Myeloproliferative Neoplasms
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: KaloBios to Wind Down Operations
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Humanigen, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2010
- Primary completion
- Jul 2016 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 29 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 dose levels: KB004 | Experimental | Drug: KB004, Monoclonal AntibodyIV 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) |
| Phase 2 dose levels: KB004 | Experimental | Drug: KB004, Monoclonal AntibodyIV infusion 1x Weekly for a 21 day dosing cycle Subjects will be assigned to the recommended Phase 2 dose of 250 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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]).
- Part A: AML or MDS patients with an acceptable level of EphA3 expression
- Part B: MF patients with an acceptable level of EphA3 expression
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KB004, Monoclonal Antibody | Drug | Phase 1 dose levels: KB004, Phase 2 dose levels: KB004 |
Primary outcome
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
4 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2015.
- Derived from this study: PubMed 27736729Swords 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Morgan Lam study director
Humanigen, Inc.
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing KB004, Monoclonal Antibody in people with Myelodysplastic Syndrome (MDS) and Myelofibrosis (MF), run by Humanigen, Inc. at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 17 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Determine a possible maximum tolerated dose (MTD) (time frame: Once weekly for the first three weeks of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01211691, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2015.