Clinical trial NCT01211691: 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
Overall status: SUSPENDED
Phase: PHASE1
PHASE2
Conditions: Myelodysplastic Syndrome (MDS)
Myelofibrosis (MF)
Keywords: Hematologic
Leukemia
Malignancies
Myeloproliferative Neoplasms
Lead sponsor: Humanigen, Inc.
Sponsor class: INDUSTRY
First posted: 2010-09-29
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Phase 1: Determine a possible maximum tolerated dose (MTD)
timeFrame: Once weekly for the first three weeks of study treatment
measure: Phase 2: To characterize preliminary clinical activity based on the International Working Group (IWG) criteria specific to the hematologic malignancy
timeFrame: Evaluations at designated timepoints
Secondary outcomes:
measure: Phase 1: Examine clinical activity
timeFrame: Evaluations at designated timepoints
measure: Phase 1/2: Safety and Tolerability
timeFrame: Duration of study participation
measure: Phase 1/2: Pharmacokinetic profile
timeFrame: Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles
measure: Phase 1/2: Assess immunogenicity
timeFrame: Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles
Other outcomes:
Locations:
city: Palo Alto
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Manhattan
country: United States
state: New York
city: Cleveland
country: United States
state: Ohio
city: Houston
country: United States
state: Texas
city: Adelaide
country: Australia
state: South Australia
city: Prahran
country: Australia
state: Victoria
Study officials:
affiliation: Humanigen, Inc.
name: Morgan Lam
role: STUDY_DIRECTOR
References:
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.