Untreated patients with higher risk MDS and oligoblastic AML eligible and intended for allogeneic HCT within the next 6 months MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: HLT Classification code 10028536 Term: Myelodysplastic syndromes System Organ Class: 100000004851
Conditions
Interventions
Trade Name: Vyxeos
Product Name: Vyxeos
Product Code: CPX351
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: DAUNORUBICIN
CAS Number: 20830-81-3
Concentration unit: mg/m2 mi
Sponsors
GWT-TUD GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult patients, 18-75 years of age 2. Diagnosis of high risk MDS including oligoblastic non-proliferative (WBC 6 months prior to Day-1) and are to be used throughout the entire study period and for 6 months following the last dose of CPX-351. - Male patients must be willing to refrain from sperm donation for 6 months following the last dose of CPX-351 and must use adequate contraception throughout the entire study period and for 6 months following the last dose of CPX-351. - Combined oral contraceptive pills are not recommended. It is recommended that during the study two medically accepted methods of contraception (e.g. as hormonal contraceptive methods along with a condom) apply. †A female subject or a female partner of a male subject is considered to have childbearing potential unless she meets at least one of the following criteria: Age =50 years and naturally amenorrhoeic for = 1 year (amenorrhoea following cancer therapy does not rule out childbearing potential), premature ovarian failure confirmed by a specialist gynecologist, previous bilateral salpingo-oophorectomy or hysterectomy, XY genotype, Turner syndrome or uterine agenesis. 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 135 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible. 2. WHO-2016 defined AML entities: AML with t(15;17), PML-RARA; AML with t(8;21), RUNX1-RUNX1T1, AML with inv(16)/t(16;16), CBFß-MYH11; AML with BCR-ABL1, AML with biallelic CEBPA mutation; AML with mutated FLT3 or NPM1. 3. Clinical evidence of active CNS leukaemia (assessment of CSF is not mandatory for screening). 4. Patients with a “currently active” second malignancy other than non-melanoma skin cancers. Patients are not considered to have a “currently active” malignancy if they have completed therapy more than 2 years ago and are disease free. 5. Any major surgery or radiation therapy within four weeks prior screening. 6. Patients with prior treatment of either CPX-351, hypomethylating agents, cytarabine or intensive chemotherapy for high-risk MDS or AML. 7. Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent). 8. Recent (<30 days) or planned live vaccinations during the clinical trial 9. Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent. 10. Creatinine clearance < 30 ml/min 11. Active or uncontrolled infection. Patients with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for =72 hrs. 12. Current evidence of invasive fungal infection (blood or tissue culture); patients with recent fungal infection must have a subsequent negative cultures to be eligible; known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values). 13. Hypersensitivity to cytarabine, daunorubicin or liposomal products. 14. History of Wilson’s disease or other copper-metabolism disorder, unless the therapy outweighs the risks. 15. Female patients who are pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the event-free survival (EFS) at 2 years of CPX-351 vs. CCR before allogeneic blood cell transplantation (alloHCT) as first line treatment in patients with higher risk MDS and oligoblastic AML.;Secondary Objective: • To compare best and overall response of CPX-351 vs. CCR • To compare the safety and tolerability of CPX-351 vs. CCR • To compare the effects of CPX-351 vs. CCR on the proportion of patients proceeding to alloHCT • To compare the effect of CPX-351 vs. CCR on minimal residual disease (MRD) • To compare the effect of CPX-351 vs. CCR on quality of life;Primary end point(s): 2-year EFS in both arms;Timepoint(s) of evaluation of this end point: After LPLV (EOS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Best and overall response rate according to AML-ELN and MDS-IWG criteria • Toxicity as measured by NCI CTCAE v5.0 • Proportion of patients proceeding to alloHCT • Overall survival at 2 years • MRD assessed at all times of BM puncture • Quality of life as measured by EORTC-QLQ30 supplemented by information on self-assessed concomitant diseases and demographics upon inclusion and at EOT (i.e. before alloHCT, if applicable);Timepoint(s) of evaluation of this end point: After LPLV (EOS) | — |
Countries
Austria, Germany
Contacts
Public ContactEMSCO
GWT-TUD GmbH
Outcome results
None listed