Clinical trial NCT02115672: Imatinib and BL-8040 (Novel Anti CXCR4 Antagonist) for Improving Molecular Response in Chronic Myelogenous Leukemia
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.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Chronic Myeloid Leukemia
Keywords: Chronic myeloid leukemia
imatinib
CXCR4 antagonist
BL-8040
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2014-04-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: To assess the safety and tolerability of BL-8040 in combination with Imatinib in CML patients
timeFrame: 4 months
Secondary outcomes:
measure: To assess the clinical efficacy of BL-8040 in combination with Imatinib
timeFrame: 2 years
Other outcomes:
measure: To assess additional pharmacodynamic parameters relevant to CXCR4 inhibition
timeFrame: 2 months
Locations:
city: Tel-Hashomer
country: Israel
facility: Chaim Sheba Medical Center
Study officials:
affiliation: Chaim Sheba Medical Center
name: Arnon Nagler, MD
role: PRINCIPAL_INVESTIGATOR
References: