Imatinib and BL-8040 (Novel Anti CXCR4 Antagonist) for Improving Molecular Response in Chronic Myelogenous Leukemia

Chronic Myeloid Leukemia Clinical Trial

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.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02115672
• Other study ID #: SHEBA-13-0575-AN-CTIL
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: April 14, 2014
• Last updated: August 11, 2016
• Start date: November 2014
• Est. completion date: November 2018

Study information

• Verified date: December 2014
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2018
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• BL-8040
BL-8040 will be added to imatinib to improve CML response.

Locations

Country	Name	City	State
Israel	Chaim Sheba Medical Center	Tel-Hashomer

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To assess additional pharmacodynamic parameters relevant to CXCR4 inhibition	The investigators will test CXCR4 receptor occupancy and expression and additional pharmacodynamic endpoints relevant to CXCR4 inhibition.	2 months	No
Primary	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.	4 months	Yes
Secondary	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.	2 years	No