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

NCT01838395 | Completed Phase 2 Results DMC

• 1 other identifier: BL-8040.01
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 10

Brief Summary

A study is designed to assess if BL-8040 in combination with cytarabine (Ara-C) can help controlling the disease in patients with Acute Myeloid Leukemia (AML) that have relapsed or did not respond adequately to previous treatment. The safety of the study drug combination will also be studied.

Conditions

Acute Myeloid Leukemia

Keywords

AML; Acute Myeloid Leukemia; Relapsed Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

  Number of participants with Adverse event affecting the safety and tolerability of BL-8040 + Ara-C by dose level (overall, dose limiting events, related Adverse Events (AEs), Serious Adverse Events (SAEs), related SAEs, AE by severity and death) Toxicity grade was assessed according to version V4.03 of NCI-CTCAE

  Participants were followed for the duration of the hospital stay and the follow-up period, an expected average of 6 weeks.

Secondary Outcomes (7)

• Response to Treatment by Dose

  Final bone marrow evaluation - Between Day 20 and Day 44

• Apoptotic Effect

  Final evaluation - between Day 20 and Day 44

• Assessment of the Pharmacokinetic Profile of BL-8040 - t1/2 (h)

  Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1.

• Assessment of the Pharmacokinetic Profile of BL-8040 - Tmax (h)

  Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1.

• Assessment of the Pharmacokinetic Profile of BL-8040 - Cmax (ng/mL)

  Blood samples for the determination of BL-8040 were collected before dosing and at 0.25, 0.5, 1, 2, 4, 8, and 24 hours after BL-8040 administration on Day 1.

Study Arms (6)

BL-8040 0.5mg/kg + Ara-C 1.5 or 3 g/m2/d per dose (based on age)

EXPERIMENTAL

Arm 1: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 0.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days.

Drug: Ara-C; Drug: BL-8040

BL-8040 0.75mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age)

EXPERIMENTAL

Arm 2: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 0.75 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days.

Drug: Ara-C; Drug: BL-8040

BL-8040 1.0mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age)

EXPERIMENTAL

Arm 3: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 1 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days.

Drug: Ara-C; Drug: BL-8040

BL-8040 1.25mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age)

EXPERIMENTAL

Arm 4: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 1.25 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days.

Drug: Ara-C; Drug: BL-8040

BL-8040 1.5mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age)

EXPERIMENTAL

Arm 5: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 1.5 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days.

Drug: Ara-C; Drug: BL-8040

BL-8040 2mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age)

EXPERIMENTAL

Arm 6: Participants will be dosed with SC injections of BL-8040 over two days followed by concurrent administration of 2 mg/kg BL-8040 with cytarabine (Ara-C) 1.5 or 3 g/m2/d per dose (based on age) during 5 days.

Drug: Ara-C; Drug: BL-8040

Interventions

Ara-C DRUG

IV (intravenous administration)

Also known as: Cytarabine

BL-8040 0.5mg/kg + Ara-C 1.5 or 3 g/m2/d per dose (based on age); BL-8040 0.75mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age); BL-8040 1.0mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age); BL-8040 1.25mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age); BL-8040 1.5mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age); BL-8040 2mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age)

BL-8040 DRUG

SC (subcutaneous injection)

BL-8040 0.5mg/kg + Ara-C 1.5 or 3 g/m2/d per dose (based on age); BL-8040 0.75mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age); BL-8040 1.0mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age); BL-8040 1.25mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age); BL-8040 1.5mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age); BL-8040 2mg/kg + Ara-C 1.5 or 3 g/m2/d (based on age)

Eligibility Criteria

• Age: 18 Years - 75 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 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:
• White Blood Cells (WBC) \< 30,000/mL Blasts in Peripheral Blood (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.

You may not qualify if:

• 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 Tumor Lysis Syndrome (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 ( Alanine Transaminase (ALT)/Serum Glutamic Pyruvic Transaminase (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.

Sponsors & Collaborators

• BioLineRx, Ltd.: lead

Study Sites (10)

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Meir Medical Center

Kfar Saba, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; 4-fluorobenzoyl-TN-14003

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: VP Clinical & Medical Affairs
• Organization: BioLineRx Ltd.

clinicaltrials@biolinerx.com

+972-8-642-9100

Study Officials

• Arnon Aharon, MD

  BioLineRx, Ltd.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study (Part 1) will include escalating dose groups and be considered the 'escalation phase'. Five potential 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 and evaluated for dose escalation. Dose escalation will be permitted until the Maximum 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 5 (1.5 mg/kg).

Study Record Dates

• First Submitted: April 14, 2013
• First Posted: April 24, 2013
• Study Start: April 1, 2013
• Primary Completion: March 1, 2016
• Study Completion: July 20, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-08

Locations

US (5); IL (5)