Study of KB004 in Subjects With Hematologic Malignancies (Myelodysplastic Syndrome, MDS, Myelofibrosis, MF)

NCT ID: NCT01211691

Last Updated: 2015-11-17

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2016-12-31

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

Conditions

Myelodysplastic Syndrome (MDS); Myelofibrosis (MF)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 dose levels: KB004

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)

Group Type: EXPERIMENTAL

KB004, Monoclonal Antibody

Intervention Type: DRUG

Phase 2 dose levels: KB004

IV infusion 1x Weekly for a 21 day dosing cycle

Subjects will be assigned to the recommended Phase 2 dose of 250 mg

Group Type: EXPERIMENTAL

KB004, Monoclonal Antibody

Intervention Type: DRUG

Interventions

KB004, Monoclonal Antibody

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Humanigen, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Morgan Lam

Role: STUDY_DIRECTOR

Humanigen, Inc.

Locations

Palo Alto, California, United States

Sacramento, California, United States

Miami, Florida, United States

Tampa, Florida, United States

Manhattan, New York, United States

Cleveland, Ohio, United States

Houston, Texas, United States

Adelaide, South Australia, Australia

Prahran, Victoria, Australia

Countries

United States; Australia

References

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.

Reference Type: DERIVED

PMID: 27736729 (View on PubMed)

Other Identifiers

KB004-01

Identifier Type: -

Identifier Source: org_study_id