Bisantrene Combination for Resistant AML

Last updated: November 27, 2023
Sponsor: Sheba Medical Center
Overall Status: Active - Recruiting

Phase

2

Condition

Leukemia

Treatment

Bisantrene

Fludarabine

Clofarabine

Clinical Study ID

NCT04989335
RAC-002
  • Ages 18-65
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved writtenInformed 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) andhave 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, alanineaminotransferase (ALT) or aspartate aminotransferase (AST) ≤4 × the upper limit ofnormal (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), andany 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 recoveredto Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
  11. Females must be surgically or biologically sterile or postmenopausal (amenorrhoeic forat least 12 months) or if of childbearing potential, must have a negative urine orserum pregnancy test within 14 days before study entry, and must agree to use anadequate method of contraception, i.e. barrier method, during the study until 30 daysafter the last treatment. Males must be surgically or biologically sterile or agree touse an adequate method of contraception, i.e. barrier method, during the study until 30 days after the last treatment.

Exclusion

Exclusion Criteria:

  1. Acute promyelocytic leukemia (APML, APL) M3 subtype of AML.
  2. Other active malignancy (including other hematologic malignancies) or other malignancywithin the last 12 months except non-melanoma skin cancer or cervical intraepithelialneoplasia.
  3. Prior or current therapy:
  4. Hydroxyurea or other oral medications to reduce blast count within 72 hoursbefore the first dose of study drug
  5. Treatment with an investigational agent within 14 days before the first dose ofstudy drug, or not recovered from all acute effects of previous investigationaltherapy
  6. 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 toenrollment
  7. For patients who have undergone hematopoietic stem cell transplantation (HSCT),procedure-related medications (e.g. immunosuppressive therapy) administered within 2weeks prior to first dose of study drug.
  8. Any medical, psychological, or social condition that may interfere with studyparticipation or compliance or may compromise the patient's safety in the opinion ofthe investigator.

Study Design

Total Participants: 29
Treatment Group(s): 3
Primary Treatment: Bisantrene
Phase: 2
Study Start date:
August 02, 2021
Estimated Completion Date:
December 01, 2025

Connect with a study center

  • Chaim Sheba Medical Center

    Ramat Gan, 57261
    Israel

    Active - Recruiting

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