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

Sponsor

Humanigen, Inc. (Industry)

Overall Status

Suspended

CT.gov ID

NCT01211691

Collaborator

(none)

120

Enrollment

Locations

Arms

Duration (Months)

13.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome (MDS) Myelofibrosis (MF)	Drug: KB004, Monoclonal Antibody	Phase 1/Phase 2

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

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Study of the Anti-EphA3 Monoclonal Antibody KB004 in Subjects With EphA3-Expressing Hematologic Malignancies

Study Start Date :

Sep 1, 2010

Anticipated Primary Completion Date :

Jul 1, 2016

Anticipated Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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)	Drug: KB004, Monoclonal Antibody
Experimental: 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	Drug: KB004, Monoclonal Antibody

Arm

Intervention/Treatment

Experimental: 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)

Drug: KB004, Monoclonal Antibody

Experimental: 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

Drug: KB004, Monoclonal Antibody

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Palo Alto	California	United States	94304
2	Sacramento	California	United States	95817
3	Miami	Florida	United States	33136
4	Tampa	Florida	United States	33612
5	Manhattan	New York	United States	10029
6	Cleveland	Ohio	United States	44195
7	Houston	Texas	United States	77030
8	Adelaide	South Australia	Australia	5000
9	Prahran	Victoria	Australia	3007