loss of support

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.

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.

Inclusion Criteria:

1. Adult men and women subjects aged 18 to 70, inclusive.

2. Confirmed diagnosis of chronic phase CML according to the WHO criteria (WHO 2008)

3. 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

4. Clinical laboratory values should be as follows:

   White blood cell count < 30 X 10*9/L Creatinine < 1.5 ULN

5. Women of childbearing potential and all men must agree to use approved form of contraception

6. Subject is able and willing to comply with the requirements of the protocol.

7. Subject is able to voluntarily provide written informed consent.

Exclusion Criteria:

1. CML patients not in chronic phase.

2. CML patients receiving Tyrosine Kinase Inhibitors other than Imatinib.

3. CML patients receiving Imatinib > 400 mg/day.

4. Patients not able to sign informed consent.

5. Known allergy or hypersensitivity to any of the test compounds or materials or contraindication to test product.

6. Low Performance Status (ECOG > 2).

7. Abnormal liver function tests:

   1. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) 2 x upper limit of normal (ULN).
   2. Serum bilirubin. Total bilirubin > 2.0 mg/dL (34 µmol/L), conjugated bilirubin > 0.8 mg/dL

8. Abnormal left ventricular ejection fraction, < 40 %.

9. Subject has concurrent, uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place him/her at unacceptable risk, including, but not limited to:

   1. 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
   2. A co-morbid condition which, in the view of the Investigators, renders the subject at high risk from treatment complications.

10. Women subjects who are pregnant or breastfeeding.