Vyxeos for Induction of Low- or Intermediate-risk.

• Status: Recruiting
• Trial end date: 2027-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Vyxeos Vyxeos is a liposomal-encapsulated combination of cytarabine and daunorubicin, at a molar ratio of 5:1. Delivery of the 5:1 molar ratio seems to prevent antagonistic drug-drug interactions and the liposomal encapsulation increases the plasma half-life of cytarabine and daunorubicin and leads to drug accumulation within the bone marrow (BM).

Despite previous results that highlighted the advantage of Vyxeos for sAML, it is intuitively likely that this powerful drug is also suitable for non-sAML. The mechanism of action is relevant for every AML. Following the FDA approval of the drug for sAML we would like to evaluate its efficacy for low or intermediate risk fms-like tyrosine kinase 3 (FLT3)-negative de novo AML patients. This consideration is particularly relevant by the inclusion of young AML patients in the study.

Gemtuzumab ozogamicin (GO) Gemtuzumab ozogamicin (Mylotarg) - an anti-cluster of differentiation 33 (CD33) monoclonal antibody linked to calicheamicin, was approved for the treatment of newly diagnosed AML patients, when given as a combination with the '7+3' regimen.

One of the goals of the current study is to examine the feasibility and efficacy of the combination of Mylotarg plus Vyxeos.

Minimal/ measurable residual disease (MRD) Minimal or measurable residual disease (MRD) denotes the presence of leukemia cells down to levels of 1:10-4 to 1:10-6, compared with 1:20 in morphology-based assessments. MRD can be evaluated using a variety of multiparameter flow cytometry (MFC) and molecular methods. There are no data regarding the achievement or impact of MRD using Vyxeos as induction therapy. The current trial will address this issue.

Purpose of this Trial The current study is designed to examine the response rate of the Vyxeos as induction therapy for newly diagnosed low/intermediate risk AML patients in the 'real world' setting. Patients will receive the same induction therapy that they were to receive had they not entered this study (cytarabine /daunorubicin ± Mylotarg) but the combination of cytarabine /daunorubicin will be given in the unique formulation of Vyxeos. In addition to classic CR+CRi evaluation, MFC MRD evaluation, using an centralized, internationally recognized laboratory, will be done at the end of induction. In addition, this pilot study will also provide clinical safety information about the combination of Vyxeos with Mylotarg.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shaare Zedek Medical Center
• Treatments: Gemtuzumab

Criteria

Inclusion criteria:

1. Diagnosis of AML (>20% blasts in blood or BM)

2. Favorable or intermediate risk cytogenetics

Exclusion criteria:

1. Acute promyelocytic leukemia with recurring translocations involving Retinoic Acid Receptor Alpha (RARA)

2. Acute leukemias of ambiguous lineage

3. Therapy-related myeloid neoplasms

4. Background of myelodysplastic syndrome or myeloproliferative neoplasm

5. FLT3-Internal tandem duplications (ITD) mutation with any allelic ratio

6. AML with Adverse cytogenetic risk (ELN 2017)

7. Eastern Cooperative Oncology Group (ECOG) performance status 3-4

8. Previous treatment with radiation therapy or cytotoxic chemotherapy (treatment with corticosteroids or hydroxyurea will not exclude the patient)

9. Age<18 or >70

10. Serum creatinine ≥ 2.0 mg/dl or creatinine clearance < 50 ml/min within 14 days of registration

11. Direct bilirubin ≥2.0 g/dl, or alkaline phosphatase/ serum glutamic-oxaloacetic transaminase (SGOT) > 4xupper limit of normal within 14 days of registration

12. Left ventricular ejection fraction (LVEF)<45%

13. Pregnant or breastfeeding women

14. Blastic transformation of chronic myelogenous leukemia (CML)

15. Secondary AML (defined as prior chemotherapy-induced or evolved from myelodysplastic syndrome or myeloproliferative neoplasm)