Myelodysplastic Syndrome (MDS), Myelofibrosis (MF)
Conditions
Keywords
Hematologic, Leukemia, Malignancies, Myeloproliferative Neoplasms
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
Interventions
DRUGKB004, Monoclonal Antibody
Sponsors
Humanigen, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1: Determine a possible maximum tolerated dose (MTD) | 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 | Evaluations at designated timepoints |
Secondary
| Measure | Time frame |
|---|---|
| Phase 1: Examine clinical activity | Evaluations at designated timepoints |
| Phase 1/2: Safety and Tolerability | Duration of study participation |
| Phase 1/2: Pharmacokinetic profile | Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles |
| Phase 1/2: Assess immunogenicity | Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles |
Countries
Australia, United States
Outcome results
None listed