Multiple MyelomaPhase 1/2NCT01010880
Safety Study of a Chemokine Receptor (CXCR4) Antagonist in Multiple Myeloma Patients
A Phase 1/2 study testing BKT140 in people with Multiple Myeloma, run by Biokine Therapeutics Ltd at 2 sites in Israel.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- BKT140
- How many people
- 16 participants
- Where
- 2 sitesIsrael
- Study dates
- Oct 2008to Jul 2010
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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%,
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 1 country.
Israel2 sites
Department of Hematology and Bone Marrow Transplantation,Rambam Medical Center
Haifa, 31096
Chaim Sheba Medical Center,Tel-Hashomer
Ramat Gan, 52621
About this study
Official title: 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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- BKT140
- Keywords
- Multiple Myeloma, CXCR4, Stem Cells, Mobilization, Transplantation, Chemotherapy
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BKT140Drug
BKT-140 drug substance is a highly selective CXCR4 antagonist. BKT140 will be injected S.C once at dose of 0.03, 0.1, 0.3, 0.9 mg/kg
What is being measured
The primary outcome is the main question the study is designed to answer.
White blood cell (WBC) count
Measured: 24 hour
Secondary outcomes (1)
CD34+ cells
Measured: 24 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2009 (estimated)
- Study startOct 2008
- Primary completionJul 2010
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Biokine Therapeutics Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Arnon Nagler, MD, Principal investigator, Chaim Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01010880
- Sponsor's protocol ID
- BKTSC001
- Status last verified
- Jun 2011
- First submitted
- 9 Nov 2009
- Last updated
- 10 Jun 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Abraham M, Biyder K, Begin M, Wald H, Weiss ID, Galun E, Nagler A, Peled A. Enhanced unique pattern of hematopoietic cell mobilization induced by the CXCR4 antagonist 4F-benzoyl-TN14003. Stem Cells. 2007 Sep;25(9):2158-66. doi: 10.1634/stemcells.2007-0161. Epub 2007 May 24.
PubMed 17525235
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIA, Non-Randomized, Open Label, Single Dose, Dose-Escalation, Safety Study of BKT140, a CXCR4 Antagonist in Patients With Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01010880
- Acronym / sponsor ID
- BKTSC001
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, CXCR4, Stem Cells, Mobilization, Transplantation, Chemotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Biokine Therapeutics LtdIndustry (pharma, biotech, devices)
- Study start
- Oct 2008
- Primary completion
- Jul 2010 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 10 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (17 listed)
- 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%)
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BKT140BKT-140 drug substance is a highly selective CXCR4 antagonist. BKT140 will be injected S.C once at dose of 0.03, 0.1, 0.3, 0.9 mg/kg | Drug | – |
Primary outcome
White blood cell (WBC) count
Time frame: 24 hour
1 secondary outcome
CD34+ cells
Time frame: 24 hour
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2011.
- Background: PubMed 17525235Abraham M, Biyder K, Begin M, Wald H, Weiss ID, Galun E, Nagler A, Peled A. Enhanced unique pattern of hematopoietic cell mobilization induced by the CXCR4 antagonist 4F-benzoyl-TN14003. Stem Cells. 2007 Sep;25(9):2158-66. doi: 10.1634/stemcells.2007-0161. Epub 2007 May 24.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arnon Nagler, MD principal investigator
Chaim Sheba Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BKT140 in people with Multiple Myeloma, run by Biokine Therapeutics Ltd at 2 sites in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
White blood cell (WBC) count (time frame: 24 hour). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01010880, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2011.