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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by KaloBios Pharmaceuticals
Information provided by (Responsible Party):
KaloBios Pharmaceuticals Identifier:
First received: September 24, 2010
Last updated: June 18, 2015
Last verified: June 2015

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 Intervention Phase
Myelodysplastic Syndrome (MDS)
Myelofibrosis (MF)
Drug: KB004, Monoclonal Antibody
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study of the Anti-EphA3 Monoclonal Antibody KB004 in Subjects With EphA3-Expressing Hematologic Malignancies

Resource links provided by NLM:

Further study details as provided by KaloBios Pharmaceuticals:

Primary Outcome Measures:
  • Phase 1: Determine a possible maximum tolerated dose (MTD) [ Time Frame: Once weekly for the first three weeks of study treatment ] [ Designated as safety issue: Yes ]
  • Phase 2: To characterize preliminary clinical activity based on the International Working Group (IWG) criteria specific to the hematologic malignancy [ Time Frame: Evaluations at designated timepoints ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Phase 1: Examine clinical activity [ Time Frame: Evaluations at designated timepoints ] [ Designated as safety issue: No ]
  • Phase 1/2: Safety and Tolerability [ Time Frame: Duration of study participation ] [ Designated as safety issue: Yes ]
  • Phase 1/2: Pharmacokinetic profile [ Time Frame: Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles ] [ Designated as safety issue: No ]
  • Phase 1/2: Assess immunogenicity [ Time Frame: Cycle 1: multiple timepoints. Thereafter, single samples at designated cycles ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: September 2010
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01211691

Contact: Clinical Trials

United States, California
Palo Alto, California, United States, 94304
Sacramento, California, United States, 95817
United States, Florida
Miami, Florida, United States, 33136
Tampa, Florida, United States, 33612
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, New York
Manhattan, New York, United States, 10029
United States, Ohio
Cleveland, Ohio, United States, 44195
United States, Texas
Houston, Texas, United States, 77030
Australia, New South Wales
Westmead, New South Wales, Australia, 2145
Australia, South Australia
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Prahran, Victoria, Australia, 3007
Australia, Western Australia
Perth, Western Australia, Australia, 6000
Queensland, Australia, 4006
Sponsors and Collaborators
KaloBios Pharmaceuticals
Study Director: Morgan Lam KaloBios Pharmaceuticals
  More Information

No publications provided

Responsible Party: KaloBios Pharmaceuticals Identifier: NCT01211691     History of Changes
Other Study ID Numbers: KB004-01
Study First Received: September 24, 2010
Last Updated: June 18, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by KaloBios Pharmaceuticals:
Myeloproliferative Neoplasms

Additional relevant MeSH terms:
Myeloproliferative Disorders
Myelodysplastic Syndromes
Primary Myelofibrosis
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs processed this record on October 07, 2015