Safety Study of a Chemokine Receptor (CXCR4) Antagonist in Multiple Myeloma Patients

June 9, 2011 updated by: Biokine Therapeutics Ltd

A Phase I/IIA, Non-Randomized, Open Label, Single Dose, Dose-Escalation, Safety Study of BKT140, a CXCR4 Antagonist in Patients With Multiple Myeloma

BKT-140 drug substance is a highly selective chemokine receptor (CXCR4) antagonist, which is developed by Biokine as a novel therapy for Multiple Myeloma (MM, a type of blood cancer). The unique combination of activities of BKT140, i.e., the induction of the exit of blood cells such as stem cells and mature cells from the bone marrow to the peripheral blood, coupled with specific induction of MM cell death by BKT-140, represents a novel therapeutic strategy against MM.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The chemokine CXCL12 (also called SDF-1 - stromal-derived-factor-1) and its receptor, CXCR4 ((CXC Chemokine Receptor 4), a molecule endowed with potent chemotactic activity for hematopoietic cells, together play a pivotal role in the trafficking of hematopoietic stem cells to the bone marrow 10,11. The CXCL12/CXCR4 axis is also critically involved in the retention of hematopoietic cells within the BM microenvironment. Following chemotherapy and irradiation, the CXCL12/CXCR4 axis delays the recovery of the BM progenitor cells and the exit of mature cells such as neutrophils and monocytes to the periphery. Consequently, disruption of the CXCL12/CXCR4 interaction results in mobilization of hematopoietic cells including stem cells and a faster recovery of the treated BM.

BKT140 (4F-benzoyl-TN14003) is a highly selective and unique CXCR4 antagonist. Pre-clinical studies showed that BKT140 binds CXCR4 with high affinity (1nM) 13. Biokine has demonstrated the ability of the CXCR4 antagonist, BKT140, to mobilize various WBC such as neutrophils and monocytes as well as progenitor and stem cells, from the BM. The ability of BKT140 to stimulate the mobilization of these cells is superior to that of AMD3100, a CXCR4 antagonist that is in clinical development for mobilization of stem cells in MM and lymphoma patients, both qualitatively and quantitatively. BKT140 synergizes much more efficiently with G-CSF when compared to AMD3100. Moreover, Biokine has shown that BKT140, in synergism with G-CSF (NEUPOGEN®), is much more efficient in increasing the numbers of neutrophils and activated monocytes in the blood, by several folds as compared to G-CSF alone. BKT140 also shortens the neutropenic period due to an early release of neutrophils and monocytes from the BM. More importantly, BKT140, in synergism with G-CSF, reduces the anemic period caused by chemotherapy, due to a RBC production, which does not occur when G-CSF is given as a sole treatment. More importantly, BKT140, but not G-CSF or AMD3100, is also capable of shortening the period of cytopenia by boosting both the recovery of all hematopoietic cells in the BM and their exit to the periphery, and therefore shortening the period of cytopenia following chemotherapy or irradiation and BM transplantation. Importantly, Biokine has shown that upon interaction with CXCR4, BKT140, but not AMD3100, selectively, specifically and rapidly stimulates human leukemia and myeloma cell death in vitro and in vivo. Furthermore, BKT140 synergizes with other chemotherapeutic agents such as rapamycine to induce MM cell death.

Study Type

Interventional

Enrollment (Anticipated)

16

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Haifa, Israel, 31096
        • Department of Hematology and Bone Marrow Transplantation,Rambam Medical Center
      • Ramat Gan, Israel, 52621
        • Chaim Sheba Medical Center,Tel-Hashomer

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 65 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males and females 18 to 65 years old inclusive
  • MM patients with clinically significant disease that achieved at least Partial Response (PR) after induction chemotherapy
  • Patients eligible for HDC with PBSC support.
  • Patients who require stem cell collection with CTX and G-CSF priming.
  • Normal LV functions (EF over 50%, DLCO over 50%)
  • Karnofsky score > 60%,

  • Patients must have normal renal and liver functions as defined below:

    • Total bilirubin ≤2.0 x institutional upper limit of normal (ULN), unless the patient has a known diagnosis of Gilbert's disease.
    • Aspartate transaminase (AST, SGOT) or alanine transaminase (ALT, SGPT) ≤3 x institutional ULN.
    • Serum creatinine ≤1.5 g/dL or calculated estimated creatinine clearance ≥40 mL/min
  • Polymorphonuclear neutrophil (PMN) count > 1,500
  • PLT >100,000
  • Hemoglobin > 9gr%
  • Women of child-bearing potential must have a negative serum or urine pregnancy test at enrollment.
  • If female, the patient is post-menopausal, surgically sterilized, or willing to use acceptable methods of birth control (e.g., hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide or abstinence) from the enrollment visit through 30 days after the administration of the study drug.
  • If male, the patient agrees to use an acceptable barrier method of contraception from the time of enrollment through 30 days after the administration of the study drug.
  • Prior to enrollment, the patient is capable of understanding the protocol and able to sign a written informed consent.

Exclusion Criteria:

  • Patients who have not achieved at least Partial Response (PR) following induction chemotherapy.
  • No pervious G-CSF therapy.
  • Creatinine clearance <40 mL /min.
  • Body temperature above 385 C on day 10.
  • Patients with blood pressure <105/60
  • Any of the following in the last 3 months prior to enrollment: Unstable Angina, Acute Myocardial Infarction (MI), Congestive Heart Failure, CVA, uncontrolled blood pressure
  • Pregnant or breast-feeding women.
  • Any medical condition which in the opinion of the Investigator places the patient at an unacceptably high risk for toxicities.
  • Treatment with any investigational agents in the last 21 days before study entry.
  • Any condition or circumstance which, in the opinion of the Investigator, would significantly interfere with the patient's protocol compliance and put the patient at increased risk.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
White blood cell (WBC) count
Time Frame: 24 hour
24 hour

Secondary Outcome Measures

Outcome Measure
Time Frame
CD34+ cells
Time Frame: 24 hour
24 hour

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biokine Therapeutics Ltd

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (ACTUAL)

July 1, 2010

Study Completion (ACTUAL)

July 1, 2010

Study Registration Dates

First Submitted

November 9, 2009

First Submitted That Met QC Criteria

November 9, 2009

First Posted (ESTIMATE)

November 10, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

June 10, 2011

Last Update Submitted That Met QC Criteria

June 9, 2011

Last Verified

June 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BKTSC001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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