Vyxeos for Induction of Low- or Intermediate-risk.

NCT05599360 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 0463-20 SZMC
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (2)

• Response rate for low/intermediate risk AML after induction with Vyxeos

  Complete Remission (CR) and Complete Remission with incomplete Hematologic Recovery (CRi) rate.

  Up to 1 month

• Safety of the combination of Vyxeos plus Mylotarg as per CTCAE v5.0.

  Number and severity of adverse events (AEs) and adverse events serious adverse events (SAEs) of participants with Vyxeos plus Mylotarg treatment. AEs and SAEs of both treatment and non-treatment-related will be collected at REDCAP project and assessed by CTCAE v5.0.

  Up to 5 years

Secondary Outcomes (4)

• MFC MRD level after Vyxeos without Mylotarg treatment

  Up to 1 month

• MFC MRD levels after Vyxeos with Mylotarg treatment

  Up to 1 month

• Disease free survival (DFS) post Vyxeos ± Mylotarg induction therapy

  Up to 5 years

• Overall survival (OS) post Vyxeos ± Mylotarg induction therapy

  Up to 5 years

Study Arms (1)

Vyxeos

EXPERIMENTAL

Drug: Vyxeos; Drug: Mylotarg

Interventions

Vyxeos DRUG

Vyxeos (daunorubicin and cytarabine) liposome for injection

Also known as: cpx-351

Vyxeos

Mylotarg DRUG

Gemtuzumab ozogamicin is an antibody-drug conjugate (ADC) composed of the CD33-directed monoclonal antibody (hP67.6; recombinant humanized immunoglobulin \[Ig\] G4, kappa antibody produced by mammalian cell culture in non-secreting 0 (NS0) cells) that is covalently linked to the cytotoxic agent N-acetyl gamma calicheamicin. Gemtuzumab ozogamicin consists of conjugated and unconjugated gemtuzumab. The conjugated molecules differ in the number of activated calicheamicin derivative moieties attached to gemtuzumab. The number of conjugated calicheamicin derivatives per gemtuzumab molecule ranges from predominantly zero to 6, with an average of 2 to 3 moles of calicheamicin derivative per mole of gemtuzumab.

Also known as: gemtuzumab ozogamicin

Vyxeos

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AML (\>20% blasts in blood or BM)
• Favorable or intermediate risk cytogenetics

You may not qualify if:

• Acute promyelocytic leukemia with recurring translocations involving Retinoic Acid Receptor Alpha (RARA)
• Acute leukemias of ambiguous lineage
• Therapy-related myeloid neoplasms
• Background of myelodysplastic syndrome or myeloproliferative neoplasm
• FLT3-Internal tandem duplications (ITD) mutation with any allelic ratio
• AML with Adverse cytogenetic risk (ELN 2017)
• Eastern Cooperative Oncology Group (ECOG) performance status 3-4
• Previous treatment with radiation therapy or cytotoxic chemotherapy (treatment with corticosteroids or hydroxyurea will not exclude the patient)
• Age\<18 or \>70
• Serum creatinine ≥ 2.0 mg/dl or creatinine clearance \< 50 ml/min within 14 days of registration
• Direct bilirubin ≥2.0 g/dl, or alkaline phosphatase/ serum glutamic-oxaloacetic transaminase (SGOT) \> 4xupper limit of normal within 14 days of registration
• Left ventricular ejection fraction (LVEF)\<45%
• Pregnant or breastfeeding women
• Blastic transformation of chronic myelogenous leukemia (CML)
• Secondary AML (defined as prior chemotherapy-induced or evolved from myelodysplastic syndrome or myeloproliferative neoplasm)

Sponsors & Collaborators

• Shaare Zedek Medical Center: lead

Study Sites (1)

Shaare Zedek Medical Center

Jerusalem, Jerusalem, 9103102, Israel

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

CPX-351; Gemtuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Chezi Ganzel, DR

  Shaare Zedek Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Hematology Day Care

Study Record Dates

• First Submitted: January 20, 2022
• First Posted: October 31, 2022
• Study Start: August 7, 2022
• Primary Completion (Estimated): September 7, 2028
• Study Completion (Estimated): September 7, 2028
• Last Updated: December 2, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)