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

NCT ID: NCT02115672

Last Updated: 2016-08-15

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2018-11-30

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.

Conditions

Chronic Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BL-8040

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).

Group Type: EXPERIMENTAL

BL-8040

Intervention Type: DRUG

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

Interventions

BL-8040

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sheba Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arnon Nagler, MD

Role: PRINCIPAL_INVESTIGATOR

Chaim Sheba Medical Center

Locations

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Countries

Israel

Other Identifiers

SHEBA-13-0575-AN-CTIL

Identifier Type: -

Identifier Source: org_study_id