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Phase IIa Study Evaluating Safety and Efficacy of BL-8040 in Relapsed/Refractory AML Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01838395
Recruitment Status : Completed
First Posted : April 24, 2013
Last Update Posted : June 15, 2016
Information provided by (Responsible Party):
BioLineRx, Ltd.

Brief Summary:
The goal of this clinical research study is to learn if BL-8040 in combination with cytarabine (Ara-C) can help to control the disease in patients with Acute Myeloid Leukemia (AML) that has relapsed or did not respond adequately to previous treatment. The safety of the study drug combination will also be studied.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Ara-C Drug: BL-8040 Phase 2

Detailed Description:

Open-label, multicenter, phase IIa, dose escalating study in subjects with relapsed/refractory AML, defined according to WHO criteria (1), including subjects who failed chemotherapy only and those who failed previous Autologous Stem Cell Transplantation (ASCT) / Allogeneic Stem Cell Transplantation (AlloSCT), provided at least 6 months have passed from transplant.

Eligible subjects will receive subcutaneous (SC) injections of BL-8040 ("monotherapy period") over two days (one injection per day) followed by concurrent administration of BL-8040 with standard salvage chemotherapy ("combined period") over 5 days. During the "combined period," BL-8040 will be administered 4 hours prior to chemotherapy. The chemotherapy will consist of cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age), administered intravenously (IV) over 3 hours, for 5 days and will not be escalated.

The first part of the study (Part 1) will include escalating dose groups and be considered the 'escalation phase'. Six potential dose levels (see Table 1) 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 and evaluated for dose escalation.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : April 2013
Actual Primary Completion Date : March 2016
Actual Study Completion Date : June 2016

Arm Intervention/treatment
Experimental: BL-8040 + Ara-C
Eligible subjects will receive subcutaneous (SC) injections of BL-8040 ("monotherapy period") over two days (one injection per day) followed by concurrent administration of BL-8040 with standard salvage chemotherapy ("combined period") over 5 days. During the "combined period," BL-8040 will be administered 4 hours prior to chemotherapy. The chemotherapy will consist of cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age), administered intravenously (IV) over 3 hours, for 5 days and will not be escalated.
Drug: Ara-C
Other Name: cytarabine

Drug: BL-8040
Other Name: BL8040

Primary Outcome Measures :
  1. Safety and tolerability [ Time Frame: "participants will be followed for the duration of hospital stay and the follow up period, an expected average of 6 weeks. ]
    • General safety: Vital signs (oral temperature, blood pressure, pulse rate, respiratory rate and O2 saturation), 12-lead ECG and physical examination.
    • Toxicity according to the latest version of NCI-CTCAE (currently V4.03, refer to )
    • for AEs and clinical laboratory profile as follows: Screening: record and report screening results, however not considered treatment emergent AEs.

    Throughout the study: record and report all AEs and SAEs according to GCP.

Secondary Outcome Measures :
  1. Clinical efficacy [ Time Frame: Final Bone Marrow evaluation -Between day 20 and day 44 ]
    The outcome will be measured by response rates as assessed at final Bone Marrow evaluation based on Cheson 2003 criteria.

  2. Apoptotic effect [ Time Frame: Final evaluation- between day 20 and day 44 ]
    Change in leukemic cell apoptosis in Peripheral Blood and Bone Marrow.

  3. Mobilization [ Time Frame: Final evaluation- between day 20 and day 44 ]
    Mobilization of AML blasts from the bone marrow to the peripheral blood (PB) by cell counting

  4. Pharmacokinetic profile [ Time Frame: Day 0 to day 7 ]
    • Cmax - maximum BL-8040 plasma concentration
    • Tmax - time to reach the maximum BL-8040 plasma concentration
    • AUC0-t - Area under the BL-8040 plasma concentration-time curve AUC0-∞ - Area under the BL-8040 plasma concentration-time curve
    • λz - elimination rate constant, determined by linear regression t1/2 - terminal elimination half-life, defined as 0.693/λz

Other Outcome Measures:
  1. Pharmacodynamic parameters [ Time Frame: After end of study- an expected average of 6 weeks. ]
    To assess additional pharmacodynamic parameters relevant to CXCR4 inhibition by CXCR4 receptor occupancy

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Adult men and women subjects aged 18 to 75, inclusive.
  2. Confirmed diagnosis of relapsed/refractory AML (WHO criteria) Refractory subjects, up to second consecutive salvage . Relapsed subjects including first and second relapse.
  3. AML relapse > 6 months since autologous or allogeneic stem cell transplantation, provided they are in first or second relapse and:

    No active graft-versus-host disease (GVHD > grade 1). No treatment with high dose steroids for GVHD (up to 20 mg Prednisolone or equivalent, Appendix G). No treatment with immunosuppressive drugs with the exception of low dose cyclosporine and tacrolimus (blood levels of 0.5-0.6 µg/mL).

  4. Clinical laboratory values should be as follows:

    WBC < 30,000/mL Blasts in PB ≤ 20,000. Treatment with Hydroxyurea is permitted up to 24 hrs prior to BL-8040 administration to achieve blast counts < 20,000 prior to enrollment. Creatinine < 1.3 mg/dL; if Creatinine is > 1 mg/dL the Creatinine clearance should be > 40 mL/min as calculated using the Cockcroft-Gault formula.

  5. Women of childbearing potential and all men must agree to use an approved form of contraception (e.g. oral, transdermal patch, implanted contraceptives, intrauterine device, diaphragm, condom, abstinence or surgical sterility) prior to study entry and for the duration of study participation through 30 days after the last dose of BL-8040. Confirmation that female subjects are not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  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. Administration of conventional chemotherapy within 2 weeks of enrollment date. In the event that subjects have received chemotherapy > 2 weeks from the date of enrollment, they may be included provided they have recovered from the associated non-hematological toxicities to ≤ grade 1.
  2. Life expectancy of ≤ 2 months.
  3. Known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product.
  4. Use of investigational device or agents within 2 weeks of enrollment date.
  5. Low Performance Status (ECOG > 2; Appendix E).
  6. O2 saturation < 92% (on room air), evidence of TLS > grade 2 (according to the Cairo-Bishop criteria (3)) or leukostasis (2).
  7. 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.

  8. Left ventricular ejection fraction < 40 %.
  9. History of myocardial infarction or cerebrovascular accident within 6 months of enrollment date.
  10. Presence of active, uncontrolled infection.
  11. Known central nervous system disease (e.g., Alzheimer's disease).
  12. Acute promyelocytic leukemia.
  13. Exposure to high dose Ara-C within 6 months of enrollment.
  14. 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.

  15. Female subjects who are pregnant or breastfeeding.
  16. Prior clinically significant grade 3-4 non-hematological toxicity to high dose Ara-C or grade ≥ 2 of neurological toxicity.
  17. Seropositive for HIV antibodies (HIV1 and HIV2), Hepatitis C antibody (Hep C Ab) or a Hepatitis B carrier (positive for Hepatitis B surface antigen [HBsAg]).
  18. Unable to comply with study requirements in the opinion of the Investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01838395

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United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Rambam Medical Center
Haifa, Israel, 31096
Shaare Zedek Medical Center
Jerusalem, Israel, 91031
Meir Medical Center
Kfar Saba, Israel
Chaim Sheba Medical Center
Ramat Gan, Israel, 52621
Tel-Aviv Sourasky Medical Center
Tel Aviv, Israel, 64239
Sponsors and Collaborators
BioLineRx, Ltd.
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Study Chair: Arnon Aharon, MD BioLineRx, Ltd.
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Responsible Party: BioLineRx, Ltd.
ClinicalTrials.gov Identifier: NCT01838395    
Other Study ID Numbers: BL-8040.01
First Posted: April 24, 2013    Key Record Dates
Last Update Posted: June 15, 2016
Last Verified: June 2016
Keywords provided by BioLineRx, Ltd.:
Acute Myeloid Leukemia
Relapsed Acute Myeloid Leukemia
Refractory Acute Myeloid Leukemia
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs