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

NCT02115672 | Withdrawn Phase 1

• 1 other identifier: SHEBA-13-0575-AN-CTIL
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Myeloid Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

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

  2 years

Other Outcomes (1)

• To assess additional pharmacodynamic parameters relevant to CXCR4 inhibition

  2 months

Study Arms (1)

BL-8040

EXPERIMENTAL

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).

Drug: BL-8040

Interventions

BL-8040 DRUG

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

BL-8040

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sheba Medical Center: lead

Study Sites (1)

Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

4-fluorobenzoyl-TN-14003

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Arnon Nagler, MD

  Chaim Sheba Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2014
• First Posted: April 16, 2014
• Study Start: November 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2018
• Last Updated: August 15, 2016

Record last verified: 2014-12

Locations

IL (1)