- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01838395
Phase IIa Study Evaluating Safety and Efficacy of BL-8040 in Relapsed/Refractory AML Patients
A PHASE IIA, MULTICENTER, OPEN-LABEL STUDY DESIGNED TO EVALUATE THE SAFETY AND EFFICACY OF ESCALATING DOSES OF BL-8040 IN ADULT SUBJECTS WITH RELAPSED/REFRACTORY ACUTE MYELOID LEUKEMIA
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Haifa, Israel, 31096
- Rambam Medical Center
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Jerusalem, Israel, 91031
- Shaare Zedek Medical Center
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Kfar Saba, Israel
- Meir Medical Center
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Ramat Gan, Israel, 52621
- Chaim Sheba Medical Center
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Tel Aviv, Israel, 64239
- Tel-Aviv Sourasky Medical Center
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Florida
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Jacksonville, Florida, United States, 32224
- Mayo Clinic
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Maryland
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Baltimore, Maryland, United States, 21231
- Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
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Missouri
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St. Louis, Missouri, United States, 63110
- Washington University School of Medicine
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New York
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New York, New York, United States, 10065
- Memorial Sloan-Kettering Cancer Center
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Texas
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Houston, Texas, United States, 77030
- MD Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Adult men and women subjects aged 18 to 75, inclusive.
- Confirmed diagnosis of relapsed/refractory AML (WHO criteria) Refractory subjects, up to second consecutive salvage . Relapsed subjects including first and second relapse.
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).
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.
- 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.
- Subject is able and willing to comply with the requirements of the protocol.
- Subject is able to voluntarily provide written informed consent.
Exclusion Criteria:
- 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.
- Life expectancy of ≤ 2 months.
- Known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product.
- Use of investigational device or agents within 2 weeks of enrollment date.
- Low Performance Status (ECOG > 2; Appendix E).
- O2 saturation < 92% (on room air), evidence of TLS > grade 2 (according to the Cairo-Bishop criteria (3)) or leukostasis (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.
- Left ventricular ejection fraction < 40 %.
- History of myocardial infarction or cerebrovascular accident within 6 months of enrollment date.
- Presence of active, uncontrolled infection.
- Known central nervous system disease (e.g., Alzheimer's disease).
- Acute promyelocytic leukemia.
- Exposure to high dose Ara-C within 6 months of enrollment.
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.
- Female subjects who are pregnant or breastfeeding.
- Prior clinically significant grade 3-4 non-hematological toxicity to high dose Ara-C or grade ≥ 2 of neurological toxicity.
- 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]).
- Unable to comply with study requirements in the opinion of the Investigator.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
IV
Other Names:
SC
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Throughout the study: record and report all AEs and SAEs according to GCP. |
"participants will be followed for the duration of hospital stay and the follow up period, an expected average of 6 weeks.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical efficacy
Time Frame: Final Bone Marrow evaluation -Between day 20 and day 44
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The outcome will be measured by response rates as assessed at final Bone Marrow evaluation based on Cheson 2003 criteria.
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Final Bone Marrow evaluation -Between day 20 and day 44
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Apoptotic effect
Time Frame: Final evaluation- between day 20 and day 44
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Change in leukemic cell apoptosis in Peripheral Blood and Bone Marrow.
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Final evaluation- between day 20 and day 44
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Mobilization
Time Frame: Final evaluation- between day 20 and day 44
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Mobilization of AML blasts from the bone marrow to the peripheral blood (PB) by cell counting
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Final evaluation- between day 20 and day 44
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Pharmacokinetic profile
Time Frame: Day 0 to day 7
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Day 0 to day 7
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacodynamic parameters
Time Frame: After end of study- an expected average of 6 weeks.
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To assess additional pharmacodynamic parameters relevant to CXCR4 inhibition by CXCR4 receptor occupancy
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After end of study- an expected average of 6 weeks.
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Cytarabine
Other Study ID Numbers
- BL-8040.01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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