Randomized Phase III Study of Standard Intensive Chemotherapy versus Intensive Chemotherapy with CPX-351 in Adult Patients with Newly Diagnosed AML and Intermediate- or Adverse Genetics - AMLSG 30-18

Phase 1

Conditions: Patients with newly diagnosed AML and intermediate- or adverse-risk genetics (according to 2017 ELN criteria), including AML with myelodysplasia-related changes (AML-MRC) and therapy-related AML according to the World Health Organization (WHO) classification
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2018-002678-34-AT

Lead Sponsor: niversity Hospital Ulm

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 882

Inclusion Criteria

1. Patients with newly diagnosed AML and intermediate- or adverse-risk genetics (according to 2017 ELN criteria), including AML with myelodysplasia-related changes (AML-MRC) and therapy-related AML according to the World Health Organization (WHO) classification
2. Age = 18 years, no upper age limit
3. Patient considered eligible for intensive chemotherapy
4. Eastern Cooperative Oncology Group (ECOG) performance status = 2 at screening
5. Genetic assessment in AMLSG central laboratory
6. Adequate renal function as evidenced by serum creatinine = 2.0 × ULN or creatinine clearance >40 mL/min based on the Cockcroft-Gault glomerular filtration rate (GFR)
7. Adequate hepatic function as evidenced by:
o Serum total bilirubin = 1.5 × upper limit of normal (ULN) unless considered due to Gilbert's disease, or leukemic involvement following approval by the Coordinating Investigator or Co-Coordinating Investigator
o Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) = 3.0 × ULN, unless considered due to leukemic involvement following approval by the Coordinating Investigator or Co-Coordinating Investigator
8. No prior chemotherapy for AML except hydroxyurea for up to 7 days during the diagnostic screening phase for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell [WBC] counts >30x10^9/L); prior treatment of myelodysplastic syndrome with hypomethylating agents is allowed
9. Non-pregnant and non-nursing women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to randomization
(Women of childbearing potential is defined as a sexually active mature woman who has not undergone a hysterectomy or bilateral oophorectomy or who has had menses at any time in the preceding 24 consecutive months)
10. Female patients of childbearing potential must agree to avoid getting pregnant while on therapy and for 27 weeks after the last dose of study drug
11. Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or apply one highly effective method of birth control (such as IUD, bilateral tubal ligation, or partner's
vasectomy) in combination with one acceptable method of birth control at the same time (such as hormonal contraception or the male partner has to use a latex condom coated with spermicide lubricant or combined
with spermicide gel or foam) while on therapy and for 27 weeks after the last dose of study drug. Hormonal contraception is only a highly effective method of birth control in case of combined (estrogen and
progestogen containing) associated with inhibition of ovulation or progestogen-only hormonal contraception associated with inhibition of ovulation is used
12. Men must use a latex condom coated with a spermicide lubricant or combined with spermicide gel or foam during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy and must agree to avoid to father a child (while on therapy and for 6 months after the last dose of study drug). In addition,
their female partners of childbearing potential have to use a highly effective method of birth control
13. Able to understand and willing to sign an informed consent form (ICF)
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 t

Exclusion Criteria

1. AML with favorable-risk genetics according to 2017 ELN criteria:
o AML with t(8;21)(q22;q22.1), RUNX1-RUNX1T1
o AML with inv(16)(p13.1q22)/t(16;16)(p13.1;q22), CBFB-MYH11
o AML with mutated NPM1 without FLT3-ITD or with FLT3-ITD low
o AML with biallelic CEBPA mutation
2. AML with FLT3 mutation as assessed by DNA fragment analysis PCR
for FLT3-ITD and FLT3-TKD mutation. Positivity is defined as a FLT3-ITD
or FLT3-TKD / FLT3-WT ratio of = 0.05 (5%).
3. Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PMLRARA;
or one of the other pathognomonic variant chromosomal
translocations/ fusion genes
4. AML with BCR-ABL1
5. Prior treatment of myelodysplastic syndrome (MDS) with intensive
chemotherapy or bone marrow transplant with a curative intent
6. Significant active cardiac disease within 6 months prior to the start of
study treatment, including New York Heart Association (NYHA) class III
or IV congestive heart failure; myocardial infarction, unstable angina
and/or stroke; severe cardiac arrhythmias, or left ventricular ejection
fraction (LVEF) <50% by ultrasound obtained within 28 days prior to the
start of study treatment
7. Severe obstructive or restrictive ventilation disorder
8. Uncontrolled infection
9. Clinical symptoms suggestive of active central nervous system (CNS)
leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid (CSF)
during screening is only required, if there is a clinical suspicion of CNS
involvement by leukemia during screening
10. Evidence of active hepatitis B or C infection or known Human
Immunodeficiency Virus (HIV) infection
11. Patients with a currently active second malignancy. Patients are
not considered to have a currently active malignancy, if they have completed therapy and are considered by their physician to be at < 30%
risk of relapse within one year. However, subjects with the following
history/concurrent conditions are allowed:
o Basal or squamous cell carcinoma of the skin
o Carcinoma in situ of the cervix
o Carcinoma in situ of the breast
o Incidental histologic finding of prostate cancer
12. Severe neurological or psychiatric disorder interfering with ability to
give an informed consent
13. No consent for registration, storage and processing of the individual
disease characteristics and course as well as information of the family
physician about study participation
14. No consent for biobanking of patient's biological specimens
15. Current participation in any other interventional clinical study within
30 days before the first administration of the investigational product or
at any time during the study
16. Patients with prior cumulative anthracycline exposure of
daunorubicin (or equivalent) can be included but the maximum of
daunorubicin (or equivalent) dose of 550 mg/m² must not be exceeded.
Anthracycline-based therapy should be avoided until exposure to the
previous cardiotoxic agents is negligible. If this is not possible, the
patient's cardiac function should be carefully monitored and an absolute
cumulative dose of 400 mg/m² in adults can be exceeded only with great
caution. In patients who received radiation therapy to the mediastinum
the maximum of daunorubicin (or equivalent) dose of 400 mg/m² must
not be exceeded
17. Known or suspected hypersensitivity to cytarabine, daunorubicin or
liposomal products and/or any excipients
18. History of Wilson's disease or other copper-metabolism disorder
19. Receipt of live, attenuated vaccine within 30 days prior to the study
inclu

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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