A phase II study of CPX-351 monotherapy in Acute Myeloid Leukemia secondary to Myeloproliferative neoplams

Phase 1

• Conditions: newly secondary AML according to WHO 2016 classification following an antecedent of Myeloproliferative Neoplasm including Essential Thrombocythemia (ET), Polycythemia Vera (PV), primary or secondary Myelofibrosis; MedDRA version: 21.1Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2021-002042-32-FR
• Lead Sponsor: FILO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-07-20
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

1.Diagnosis of newly secondary AML according to WHO 2016 classification following an antecedent of Myeloproliferative Neoplasm including Essential Thrombocythemia (ET), Polycythemia Vera (PV), primary or secondary Myelofibrosis
2.Age > 18 years.
3.Performance status < 2 (ECOG grading).
4.Eligible for standard intensive chemotherapy
5.Absence of concomitant severe cardiovascular disease which would make intensive chemotherapy impossible, i.e. arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease, reduced left ventricular function assessed by multigated acquisition (MUGA) scan or echocardiogram.
Cardiac ejection fraction = 50% by echocardiography ou MUGA”
6.Patient must have adequate organ function as indicated by the following laboratory values:
Renal
Serum creatinine: < 2 mg/dl OR calculated creatinine clearance*: = 30 mL/min by MDRD for patients with creatinine levels > 1.5 X institutional ULN
Hepatic
Serum total bilirubin: = 2.5 X ULN OR direct bilirubin = ULN for patients with total bilirubin levels = 2 mg/dL
AST (SGOT) and ALT (SGPT): = 2.5 times ULN
Alkaline Phosphatase: = 5 X ULN, if > 2.5 X ULN, then liver fraction should be = 2.5 X ULN
*Creatinine clearance should be calculated per institutional standard
7.Life expectancy should be of 12 weeks at least according to investigator evaluation.
8.Female patients of childbearing potential must have a negative serum pregnancy test (ß-hCG) within 72 hours prior to receiving the first dose of CPX-351. Female patients who are not post-menopausal, free from menses for > 2 years or surgically sterilized, will have to use adequate barrier methods of contraception to prevent pregnancy or agree to abstain from becoming pregnant throughout the study, starting with Visit 1.
9.Male patients agree to use an adequate method of contraception for the duration of the study. Men should be advised not to father a child while receiving CPX-351 and for 3 months post study.
10.Patients have the ability to understand and willingness to sign an informed consent form indicating the investigational nature of the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 42

Exclusion Criteria

Exclusion criteria
1.MPN/MDS mixed types
2.Prior therapy for AML transformation except for Hydroxyurea
3.Prior treatment with growth factors such as erythropoietin alfa (EPO) or granulocyte colony-stimulating factor (G-CSF), low-dose oral chemotherapy or Hypomethylating agents chemotherapy given in the chronic phase of MPN in the 30 days before inclusion, except for hydroxyurea.
4.Uncontrolled undercurrent illness or circumstances that could limit compliance with the study, including but not limited to the following: symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, pancreatitis, or psychiatric or social conditions that may interfere with patient compliance.
5.Active and uncontrolled infection.
6.Current participation or participation in a study with an investigational compound or device within 30 days of initial dosing with study drug.
7.Patients with acute promyelocytic leukemia
8.Known human immunodeficiency virus (HIV) infection or HIV-related malignancy.
9.Clinically active hepatitis B or hepatitis C infection.
10.Known allergy or hypersensitivity to any component of CPX-351.
11.Currently active second malignancy, other than non-melanoma skin cancer and in situ carcinoma of the cervix. Patients are not considered to have a currently active malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for >3 years or are considered by their physician to be at less than 30% risk of relapse.
12.Clinical evidence of CNS leukemia.
13.Pregnancy or breastfeeding during the projected duration of the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified