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

Humanigen

Status and phase: Suspended; Phase 2; Phase 1

Conditions: Myelofibrosis (MF); Myelodysplastic Syndrome (MDS)

Treatments: Drug: KB004, Monoclonal Antibody

Study type: Interventional

Funder types: Industry

Identifiers

NCT01211691

KB004-01

Details and patient eligibility

About

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.

Full 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

Enrollment: 120 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

Phase 1 dose levels: KB004

Experimental group

Description:

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)

Treatment:

Drug: KB004, Monoclonal Antibody

Phase 2 dose levels: KB004

Experimental group

Description:

IV infusion 1x Weekly for a 21 day dosing cycle Subjects will be assigned to the recommended Phase 2 dose of 250 mg

Treatment:

Drug: KB004, Monoclonal Antibody