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

Myelodysplastic Syndrome (MDS) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT01211691
• Other study ID #: KB004-01
• Status: Suspended
• Phase: Phase 1/Phase 2
• First received: September 24, 2010
• Last updated: November 13, 2015
• Start date: September 2010
• Est. completion date: December 2016

Study information

• Verified date: November 2015
• Source: KaloBios Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 120
• Est. completion date: December 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Myelofibrosis (MF)
• Preleukemia
• Primary Myelofibrosis

Intervention

Drug:
• KB004, Monoclonal Antibody

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
KaloBios Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Determine a possible maximum tolerated dose (MTD)		Once weekly for the first three weeks of study treatment	Yes
Primary	Phase 2: To characterize preliminary clinical activity based on the International Working Group (IWG) criteria specific to the hematologic malignancy		Evaluations at designated timepoints	Yes
Secondary	Phase 1: Examine clinical activity		Evaluations at designated timepoints	No
Secondary	Phase 1/2: Safety and Tolerability		Duration of study participation	Yes
Secondary	Phase 1/2: Pharmacokinetic profile		Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles	No
Secondary	Phase 1/2: Assess immunogenicity		Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles	Yes