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Trial record 1 of 11 for:    Sheba | Chronic Myeloid Leukemia | Israel
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Imatinib and BL-8040 (Novel Anti CXCR4 Antagonist) for Improving Molecular Response in Chronic Myelogenous Leukemia

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ClinicalTrials.gov Identifier: NCT02115672
Recruitment Status : Withdrawn (loss of support)
First Posted : April 16, 2014
Last Update Posted : August 15, 2016
Sponsor:
Information provided by (Responsible Party):
Sheba Medical Center

Tracking Information
First Submitted Date  ICMJE April 14, 2014
First Posted Date  ICMJE April 16, 2014
Last Update Posted Date August 15, 2016
Study Start Date  ICMJE November 2014
Estimated Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2014)
To assess the safety and tolerability of BL-8040 in combination with Imatinib in CML patients [ Time Frame: 4 months ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 14, 2014)
To assess the safety and tolerability of BL-8040 in combination with Imatinib in CML patients [ Time Frame: 4 months ]
We will assess the safety of the BL-8040 by grading of toxicities according to standard CTCAE criteria.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2014)
To assess the clinical efficacy of BL-8040 in combination with Imatinib [ Time Frame: 2 years ]
The cytogenetic and molecular response will be assessed by standard FISH and PCR test according to established criteria.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 8, 2014)
To assess additional pharmacodynamic parameters relevant to CXCR4 inhibition [ Time Frame: 2 months ]
The investigators will test CXCR4 receptor occupancy and expression and additional pharmacodynamic endpoints relevant to CXCR4 inhibition.
Original Other Pre-specified Outcome Measures
 (submitted: April 14, 2014)
To assess additional pharmacodynamic parameters relevant to CXCR4 inhibition [ Time Frame: 2 months ]
We will test CXCR4 receptor occupancy and expression and additional pharmacodynamic endpoints relevant to CXCR4 inhibition.
 
Descriptive Information
Brief Title  ICMJE Imatinib and BL-8040 (Novel Anti CXCR4 Antagonist) for Improving Molecular Response in Chronic Myelogenous Leukemia
Official Title  ICMJE 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Myeloid Leukemia
Intervention  ICMJE Drug: BL-8040
BL-8040 will be added to imatinib to improve CML response.
Study Arms  ICMJE Experimental: 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).
Intervention: Drug: BL-8040
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: August 11, 2016)
0
Original Estimated Enrollment  ICMJE
 (submitted: April 14, 2014)
24
Estimated Study Completion Date  ICMJE November 2018
Estimated Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02115672
Other Study ID Numbers  ICMJE SHEBA-13-0575-AN-CTIL
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sheba Medical Center
Study Sponsor  ICMJE Sheba Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Arnon Nagler, MD Chaim Sheba Medical Center
PRS Account Sheba Medical Center
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP