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

Primary Purpose

Chronic Myeloid Leukemia

Status

Withdrawn

Phase

Phase 1

Locations

Israel

Study Type

Interventional

Intervention

BL-8040

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia focused on measuring Chronic myeloid leukemia, imatinib, CXCR4 antagonist, BL-8040

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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 10*9/L Creatinine < 1.5 ULN
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.

Exclusion Criteria:

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).
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
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:
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.
Women subjects who are pregnant or breastfeeding.

Sites / Locations

Chaim Sheba Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BL-8040

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT02115672

First Posted

April 14, 2014

Last Updated

August 11, 2016

Sponsor

Sheba Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT02115672

Brief Title

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

2. Study Status

Record Verification Date

December 2014

Overall Recruitment Status

Withdrawn

Why Stopped

loss of support

Study Start Date

November 2014 (undefined)

Primary Completion Date

November 2016 (Anticipated)

Study Completion Date

November 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sheba Medical Center

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Myeloid Leukemia

Keywords

Chronic myeloid leukemia, imatinib, CXCR4 antagonist, BL-8040

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BL-8040

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

BL-8040

Intervention Description

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

Primary Outcome Measure Information:

Title

To assess the safety and tolerability of BL-8040 in combination with Imatinib in CML patients

Description

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.

Time Frame

4 months

Secondary Outcome Measure Information:

Title

To assess the clinical efficacy of BL-8040 in combination with Imatinib

Description

The cytogenetic and molecular response will be assessed by standard FISH and PCR test according to established criteria.

Time Frame

2 years

Other Pre-specified Outcome Measures:

Title

To assess additional pharmacodynamic parameters relevant to CXCR4 inhibition

Description

The investigators will test CXCR4 receptor occupancy and expression and additional pharmacodynamic endpoints relevant to CXCR4 inhibition.

Time Frame

2 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 10*9/L Creatinine < 1.5 ULN 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. Exclusion Criteria: 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). 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Arnon Nagler, MD

Organizational Affiliation

Chaim Sheba Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Chaim Sheba Medical Center

City

Tel-Hashomer

ZIP/Postal Code

52621

Country

Israel

12. IPD Sharing Statement

Learn more about this trial

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

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