Bisantrene Combination for Resistant AML

NCT ID: NCT04989335

Last Updated: 2023-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-02

Study Completion Date

2025-12-01

Brief Summary

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An Open-label, Phase II, Two-stage, Study of Xantrene® (Bisantrene) in combination with Fludarabine and Clofarabine as Salvage Therapy for Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML) Lead-in stage: up to 12 (up to 2 cohorts in a 3+3 dose escalation design) Efficacy stage: up to 17 (Simon 2-stage design 9+8)

Study Objectives:

* Confirm safety and tolerability of the combination regimen
* Time to response with combination treatment
* Overall survival

The treatment regimen will comprise daily IV infusion of Fludarabine (Flu), Clofarabine (Clo) and Bisantrene (Xan) administered via central venous line and controlled-rate infusion pump with a 1-hour break between each agent infusion, amounting to a total of 6 hours for each daily FluCloXan treatment in the following sequence:

* First, infusion over 60 minutes of Fludarabine (Flu) at 10 mg/m2
* Followed by infusion of Clofarabine (Clo) at 30 mg/m2 over 60 minutes
* Followed by infusion of Bisantrene (Xan) at 250 mg/m2 over 2 hours. One cycle will comprise daily IV infusion of the combination treatment course for 4 or 5 consecutive days and rest period to between Day 30 and Day 42, based on patient performance and disease status.

Detailed Description

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Conditions

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Myelogenous Leukemia, Acute

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Bisantrene combined with Fludarabine and Clofarabine

Bisantrene 250 mg at final concentration of 0.5 mg/mL will be administrated by intravenous (IV) infusion, delivered by a controlled-rate programmable pump via a central line over 2 hours.

Fludarabine (generic) and Clofarabine (generic) are commercially available as injection for intravenous infusion.

The treatment regimen will comprise daily IV infusion of Fludarabine (Flu), Clofarabine (Clo) and Bisantrene (Xan) administered via central venous line and controlled-rate infusion pump with a 1-hour break between each agent infusion, amounting to a total of 6 hours for each daily FluCloXan treatment in the following sequence:

* First, infusion over 60 minutes of Fludarabine (Flu) at 10 mg/m2
* Followed by infusion of Clofarabine (Clo) at 30 mg/m2 over 60 minutes
* Followed by infusion of Bisantrene (Xan) at 250 mg/m2 over 2 hours.

Group Type EXPERIMENTAL

Bisantrene

Intervention Type DRUG

Combined escalated dose chemotherapy

Fludarabine

Intervention Type DRUG

Combined escalated dose chemotherapy

Clofarabine

Intervention Type DRUG

Combined escalated dose chemotherapy

Interventions

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Bisantrene

Combined escalated dose chemotherapy

Intervention Type DRUG

Fludarabine

Combined escalated dose chemotherapy

Intervention Type DRUG

Clofarabine

Combined escalated dose chemotherapy

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent and privacy language as per national regulations.
2. Age 18 -65 (inclusive) years
3. Diagnosis of AML by World Health Organization (WHO) classification (WHO, 2016) and have received at least one line of therapy prior to enrollment into this study.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.0
5. Life expectancy ≥ 3 months.
6. Adequate organ function as evidenced by serum total bilirubin ≤ 2.0 mg/dL, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤4 × the upper limit of normal (ULN), serum albumin \>2.8 g/dL, serum creatinine ≤2 mg/dL.
7. Cardiac ejection fraction ≥50%, assessed by 2-Dimensional echocardiogram.
8. Pulmonary function ≥50% assessed by diffusing capacity for carbon monoxide (DLCO), and any clinically significant decrease in DLCO must not be caused by infection.
9. Negative for serum markers for HIV, Hepatitis -B, -C, and HTLV-1
10. Clinically significant non-hematologic toxicity after prior chemotherapy has recovered to Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
11. Females must be surgically or biologically sterile or postmenopausal (amenorrhoeic for at least 12 months) or if of childbearing potential, must have a negative urine or serum pregnancy test within 14 days before study entry, and must agree to use an adequate method of contraception, i.e. barrier method, during the study until 30 days after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception, i.e. barrier method, during the study until 30 days after the last treatment.

Exclusion Criteria

1. Acute promyelocytic leukemia (APML, APL) M3 subtype of AML.
2. Other active malignancy (including other hematologic malignancies) or other malignancy within the last 12 months except non-melanoma skin cancer or cervical intraepithelial neoplasia.
3. Prior or current therapy:

1. Hydroxyurea or other oral medications to reduce blast count within 72 hours before the first dose of study drug
2. Treatment with an investigational agent within 14 days before the first dose of study drug, or not recovered from all acute effects of previous investigational therapy
3. Last treatment was with a drug of long elimination half-life (e.g. enasidenib), as such a wash out period 5x elimination half-life is necessary prior to enrollment
4. For patients who have undergone hematopoietic stem cell transplantation (HSCT), procedure-related medications (e.g. immunosuppressive therapy) administered within 2 weeks prior to first dose of study drug.
5. Any medical, psychological, or social condition that may interfere with study participation or compliance or may compromise the patient's safety in the opinion of the investigator.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Race Oncology Ltd

INDUSTRY

Sponsor Role collaborator

Sheba Medical Center

OTHER_GOV

Sponsor Role lead

Responsible Party

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Prof Arnon Nagler

Director Hematology Division

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Arnon Nagler, MD

Role: PRINCIPAL_INVESTIGATOR

Sheba Medical Center

Locations

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Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status RECRUITING

Countries

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Israel

Central Contacts

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Arnon Nagler, MD

Role: CONTACT

972-3-530-58-30

Facility Contacts

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Arnon Nagler, M.D.

Role: primary

+97235305830

M.D.

Role: backup

Other Identifiers

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RAC-002

Identifier Type: -

Identifier Source: org_study_id