Chronic Myeloid LeukemiaPhase 1/2NCT02115672
Imatinib and BL-8040 (Novel Anti CXCR4 Antagonist) for Improving Molecular Response in Chronic Myelogenous Leukemia
A Phase 1/2 study testing BL-8040 in people with Chronic Myeloid Leukemia, run by Sheba Medical Center at 1 site in Israel.
Trial summary
The aim of the study is to test the safety and efficacy of BL-8040 (a CXCR4 antagonist) in improving the response to imatinib in CML patients not achieving an optimal response with imatinib alone. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- BL-8040
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteIsrael
- Study dates
- Nov 2014to Nov 2018
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult men and women subjects aged 18 to 70, inclusive.
- Confirmed diagnosis of chronic phase CML according to the WHO criteria (WHO 2008)
- CML patients with sub-optimal response to Tyrosine Kinase Inhibitors, defined as "warning" in the ELN recommendations:
- Following 3 months: BCR-ABL1 > 10%, and/or Ph+ 36-95% Following 6 months: BCR-ABL1 1-10%, and/or Ph + 1-35% Following 12 months: BCR-ABL1 0.1-1 % Following 24 months: Less than MR4
- Clinical laboratory values should be as follows:
- White blood cell count < 30 X 109/L Creatinine < 1.5 ULN
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- Women of childbearing potential and all men must agree to use approved form of contraception
- Subject is able and willing to comply with the requirements of the protocol.
- Subject is able to voluntarily provide written informed consent.
Who cannot join
- CML patients not in chronic phase.
- CML patients receiving Tyrosine Kinase Inhibitors other than Imatinib.
- CML patients receiving Imatinib > 400 mg/day.
- Patients not able to sign informed consent.
- Known allergy or hypersensitivity to any of the test compounds or materials or contraindication to test product.
- Low Performance Status (ECOG > 2).
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- Abnormal liver function tests:
- Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) 2 x upper limit of normal (ULN).
- Serum bilirubin. Total bilirubin > 2.0 mg/dL (34 µmol/L), conjugated bilirubin > 0.8 mg/dL
- Abnormal left ventricular ejection fraction, < 40 %.
- Subject has concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk, including, but not limited to:
- Subject has been diagnosed or treated for another malignancy within 3 years of enrolment, except in situ malignancy, or low-risk prostate, skin or cervix cancer after curative therapy
- A co-morbid condition which, in the view of the Investigators, renders the subject at high risk from treatment complications.
- Women subjects who are pregnant or breastfeeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Study Using Imatinib and s.c. BL-8040 (Novel Anti CXCR4 Antagonist) for Improving Molecular Response in Chronic Myelogenous Leukemia (CML) Patients in First Chronic Phase Achieving Less Than Optimal Response With Imatinib.
The aim of the study is to test the safety and efficacy of BL-8040 (a CXCR4 antagonist) in improving the response to imatinib in CML patients not achieving an optimal response with imatinib alone.
Read the detailed description
To improve cytogenetic and molecular response of CML patients receiving Imatinib, who have not achieved an optimal response according to European LeukemiaNet (ELN) definitions , or MR4 after 24 months with Imatinib. This will be achieved by addition of the CXCR4 antagonist BL-8040, mobilizing CML leukemia stem cells from their protective bone marrow niche and exposing them to Imatinib and BL-8040-mediated apoptosis.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- BL-8040
- Keywords
- Chronic myeloid leukemia, imatinib, CXCR4 antagonist, BL-8040
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BL-8040Drug
BL-8040 will be added to imatinib to improve CML response.
| Study group | Role | What they receive |
|---|---|---|
| BL-8040 | Experimental | Patients with chronic phase CML on Imatinib therapy (400 mg/day) achieving less than an optimal response will be treated with sc injections of BL-8040, while continuing Imatinib. The first part of the study will include escalating dose groups. Up to 4 dose levels will be investigated starting at dose level 1. Patients will be accrued in a conventional 3+3 design. Applying this study design, the first cohort of 3 patients will be treated at dose level 1 (0.5 mg/kg) on Day 1, 15, 29 and 43. Patients will continue taking Imatinib 400 mg/day throughout the study. Dose escalation will continue until the maximal tolerated dose (MTD) is established and protocol specific stopping rules for toxicity are met. If no MTD is reached, dose escalation will continue up to dose level 4 (1.25 mg/kg). Receives: Drug: BL-8040 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety and tolerability of BL-8040 in combination with Imatinib in CML patients
The investigators will assess the safety of the BL-8040 by grading of toxicities according to standard Common Toxicity Criteria for Adverse Effects (CTCAE) criteria.
Measured: 4 months
Secondary outcomes (1)
To assess the clinical efficacy of BL-8040 in combination with Imatinib
The cytogenetic and molecular response will be assessed by standard FISH and PCR test according to established criteria.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2014 (estimated)
- Study startNov 2014
- Primary completionNov 2016 (estimated)
- Study completionNov 2018 (estimated)
Why it stopped: loss of support
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Arnon Nagler, MD, Principal investigator, Chaim Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02115672
- Sponsor's protocol ID
- SHEBA-13-0575-AN-CTIL
- Status last verified
- Dec 2014
- First submitted
- 14 Apr 2014
- Last updated
- 15 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study Using Imatinib and s.c. BL-8040 (Novel Anti CXCR4 Antagonist) for Improving Molecular Response in Chronic Myelogenous Leukemia (CML) Patients in First Chronic Phase Achieving Less Than Optimal Response With Imatinib.
- ClinicalTrials.gov ID
- NCT02115672
- Acronym / sponsor ID
- SHEBA-13-0575-AN-CTIL
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- Chronic myeloid leukemia, imatinib, CXCR4 antagonist, BL-8040
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: loss of support
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- Nov 2014
- Primary completion
- Nov 2016 (estimated)
- Study completion
- Nov 2018 (estimated)
- First posted
- 16 Apr 2014 (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.
The aim of the study is to test the safety and efficacy of BL-8040 (a CXCR4 antagonist) in improving the response to imatinib in CML patients not achieving an optimal response with imatinib alone.
Detailed description
To improve cytogenetic and molecular response of CML patients receiving Imatinib, who have not achieved an optimal response according to European LeukemiaNet (ELN) definitions , or MR4 after 24 months with Imatinib. This will be achieved by addition of the CXCR4 antagonist BL-8040, mobilizing CML leukemia stem cells from their protective bone marrow niche and exposing them to Imatinib and BL-8040-mediated apoptosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BL-8040 | Experimental | Drug: BL-8040Patients with chronic phase CML on Imatinib therapy (400 mg/day) achieving less than an optimal response will be treated with sc injections of BL-8040, while continuing Imatinib. The first part of the study will include escalating dose groups. Up to 4 dose levels will be investigated starting at dose level 1. Patients will be accrued in a conventional 3+3 design. Applying this study design, the first cohort of 3 patients will be treated at dose level 1 (0.5 mg/kg) on Day 1, 15, 29 and 43. Patients will continue taking Imatinib 400 mg/day throughout the study. Dose escalation will continue until the maximal tolerated dose (MTD) is established and protocol specific stopping rules for toxicity are met. If no MTD is reached, dose escalation will continue up to dose level 4 (1.25 mg/kg). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Adult men and women subjects aged 18 to 70, inclusive.
- Confirmed diagnosis of chronic phase CML according to the WHO criteria (WHO 2008)
- CML patients with sub-optimal response to Tyrosine Kinase Inhibitors, defined as "warning" in the ELN recommendations:
- Following 3 months: BCR-ABL1 > 10%, and/or Ph+ 36-95% Following 6 months: BCR-ABL1 1-10%, and/or Ph + 1-35% Following 12 months: BCR-ABL1 0.1-1 % Following 24 months: Less than MR4
- Clinical laboratory values should be as follows:
Key exclusion criteria (14 listed)
- CML patients not in chronic phase.
- CML patients receiving Tyrosine Kinase Inhibitors other than Imatinib.
- CML patients receiving Imatinib > 400 mg/day.
- Patients not able to sign informed consent.
- Known allergy or hypersensitivity to any of the test compounds or materials or contraindication to test product.
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 |
|---|---|---|
| BL-8040BL-8040 will be added to imatinib to improve CML response. | Drug | BL-8040 |
Primary outcome
To assess the safety and tolerability of BL-8040 in combination with Imatinib in CML patients
Time frame: 4 months
The investigators will assess the safety of the BL-8040 by grading of toxicities according to standard Common Toxicity Criteria for Adverse Effects (CTCAE) criteria.
1 secondary outcome
To assess the clinical efficacy of BL-8040 in combination with Imatinib
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2016.
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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
1 site 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 BL-8040 in people with Chronic Myeloid Leukemia, run by Sheba Medical Center at 1 site 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 9 inclusion and 14 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: withdrawn, as of the sponsor's last update on 15 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 was withdrawn before enrolling participants, so there are no results.
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?
To assess the safety and tolerability of BL-8040 in combination with Imatinib in CML patients (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Aug 2016.