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.
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
Drug | Synonyms | Arms |
---|
KB004, Monoclonal Antibody | | Phase 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
Name | Type | Description | Interventions |
---|
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) | - 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 | - 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
Last Updated
November 17, 2015