Combination therapy for resistant acute myeloid leukemia

An Open-label, Phase II, Two-stage, Study of Bisantrene(Xantrene) in Combination With Fludarabine and Clofarabine as Salvage Therapy for Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML)

This study is testing a new combination treatment for adults with tough-to-treat acute myeloid leukemia to see if it can help them feel better and live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Sheba Medical Center (other gov)
• Drugs / interventions: chemotherapy, Fludarabine
• Locations: 1 site (Ramat Gan)
• Trial ID: NCT04989335 on ClinicalTrials.gov

What this trial studies

This Phase II clinical trial evaluates the safety and efficacy of a combination treatment involving Bisantrene, Fludarabine, and Clofarabine for adult patients with relapsed or refractory acute myeloid leukemia (AML). The study is designed in two stages, with an initial lead-in phase to assess tolerability followed by an efficacy stage to measure overall survival and time to response. Patients will receive the treatment via intravenous infusion over a total of six hours each day. The trial aims to provide a new salvage therapy option for those who have not responded to previous treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 65 with a confirmed diagnosis of AML who have received at least one prior line of therapy.

Not a fit: Patients with significant comorbidities or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new effective option for patients with resistant forms of AML.

How similar studies have performed: Other studies have explored combination therapies for AML, but the specific use of Bisantrene in this context is relatively novel.

Eligibility criteria

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.

Where this trial is running

Ramat Gan

• Chaim Sheba Medical Center — Ramat Gan, Israel (RECRUITING)

Study contacts

• Principal investigator: Arnon Nagler, MD — Sheba Medical Center
• Study coordinator: Arnon Nagler, MD

Conditions: Myelogenous Leukemia, Acute, AML, Resistance relapsing ,Anti Leukemic effect , Bisantrene