Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy With CPX-351 in Adult Patients With Newly Diagnosed AML and Intermediate- or Adverse Genetics

NCT03897127 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AMLSG 30-18
• Study Type: interventional
• Target: 882
• Locations: 2 countries
• Sites: 62

Brief Summary

The trial is a randomized, open-label phase III study comparing CPX-351 vs conventional intensive induction and consolidation chemotherapy in 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. Overall survival (OS) in the restricted set of de novo patients will be the primary endpoint.

Conditions

Acute Myeloid Leukemia

Keywords

CPX-351; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS) in the restricted set of de novo patients

  2 years

Secondary Outcomes (4)

• Overall survival (OS) in the extended set of patients

  2 years

• Event-free survival (EFS) with CRi considered as response to induction therapy in both, the restricted set of de novo patients and the extended set of patients

  2 years

• Event-free survival (EFS) with CRi considered as failure of induction therapy in the restricted set of de novo patients

  2 years

• Rate of objective response in the restricted set of de novo patients

  2 months

Other Outcomes (26)

• EFS with CRi considered as failure of induction therapy in the extended set of patients

  2 years

• Response rates (CR/CRi/CRMRD-/CRiMRD-) in the extended set of patients

  2 years

• Relapse-free survival (RFS) in patients who achieved CR/CRi during induction chemotherapy

  2 years

Study Arms (2)

Standard arm

ACTIVE COMPARATOR

Drug: Cytarabine; Drug: Daunorubicin

Investigational arm

EXPERIMENTAL

Drug: CPX-351

Interventions

Cytarabine DRUG

Induction therapy: 200 mg/m2 i.v. (continuously) d1-7 Consolidation therapy: * Patients age 18-60 years o Intermediate-dose cytarabine 1500 mg/m2 i.v. q12h (3 hrs) d1-3 * Patients age \>60 years o Intermediate-dose cytarabine 1000 mg/m2 i.v. q12h (3 hrs) d1-3

Standard arm

Daunorubicin DRUG

Induction therapy: 60 mg/m2 i.v. (1 hr) d1-3

Standard arm

CPX-351 DRUG

Induction 1: o CPX-351 44 mg/m2 daunorubicin / 100 mg/m2 cytarabine \[100 U/m²\] i.v. (90 min) d1,3,5 Induction 2: o CPX-351 44 mg/m2 daunorubicin / 100 mg/m2 cytarabine \[100 U/m²\] i.v. (90 min) d1,3 Consolidation therapy: o CPX-351 29 mg/m2 daunorubicin / 65 mg/m2 cytarabine \[65 U/m²\] i.v. (90 min) d1,3

Investigational arm

Eligibility Criteria

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

You may qualify if:

• Patients with newly diagnosed AML and intermediate- or adverse-risk genetics (according to 2017 ELN criteria \[Appendix B\]), including AML with myelodysplasia-related changes (AML-MRC) and therapy-related AML according to the World Health Organization (WHO) classification
• Age ≥ 18 years, no upper age limit
• Patient considered eligible for intensive chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening
• Genetic assessment in AMLSG central laboratory
• 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)
• Adequate hepatic function as evidenced by:
• 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
• 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
• No prior chemotherapy for acute leukemia except hydroxyurea for up to 14 days during the diagnostic screening phase for the control of peripheral leukemic blasts in patients with leukocytosis (e.g., white blood cell \[WBC\] counts \>30x109/l); prior treatment of myelo-dysplastic syndrome with hypomethylating agents is allowed
• 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)
• 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
• Women of childbearing 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
• 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
• Able to understand and willing to sign an informed consent form (ICF)

You may not qualify if:

• AML with favorable-risk genetics according to 2017 ELN criteria \[Appendix B\]:
• AML with t(8;21)(q22;q22.1), RUNX1-RUNX1T1
• AML with inv(16)(p13.1q22)/t(16;16)(p13.1;q22), CBFB-MYH11
• AML with mutated NPM1 without FLT3-ITD or with FLT3-ITDlow
• AML with biallelic CEBPA mutation
• 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%).
• Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PML-RARA; or one of the other pathognomonic variant chromosomal translocations/ fusion genes
• AML with BCR-ABL1
• Prior treatment of myelodysplastic syndrome (MDS) with intensive chemotherapy or bone marrow transplant with a curative intent
• 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
• Severe obstructive or restrictive ventilation disorder
• Uncontrolled infection
• 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
• Evidence of active hepatitis B or C infection or known Human Immunodeficiency Virus (HIV) infection
• 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:

Sponsors & Collaborators

• University of Ulm: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (62)

Medizinische Universität Graz

Graz, 8036, Austria

Location

Tirol Kliniken GmbH Innsbruck

Innsbruck, 6020, Austria

Location

Ordensklinikum Linz GmbH, Elisabethinen

Linz, 4020, Austria

Location

Feldkirch, Landeskrankenhaus

Rankweil, 6830, Austria

Location

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

Hanuschkrankenhaus Wien

Vienna, 1140, Austria

Location

Klinikum Aschaffenburg

Aschaffenburg, 63739, Germany

Location

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

Location

Berlin Charite - Campus Charite Mitte

Berlin, 10117, Germany

Location

Vivantes Klinikum Am Urban

Berlin, 10967, Germany

Location

Berlin Charite - Campus Benjamin Franklin

Berlin, 12200, Germany

Location

Vivantes Klinikum Neukölln

Berlin, 12351, Germany

Location

Charité Berlin

Berlin, 13353, Germany

Location

Bochum, Augusta-Kranken-Anstalt

Bochum, 44791, Germany

Location

Knappschaftskrankenhaus Bochum-Langendreer

Bochum, 44892, Germany

Location

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Städtisches Klinikum Braunschweig gGmbH

Braunschweig, 38114, Germany

Location

Klinikum Bremen-Mitte

Bremen, 28177, Germany

Location

Klinikum Darmstadt

Darmstadt, 64283, Germany

Location

St.-Johannes-Hospital

Dortmund, 44137, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Kliniken Essen Süd, Ev. Krankenhaus Essen- Werden gGmbH

Essen, 45239, Germany

Location

Klinikum Esslingen

Esslingen am Neckar, 73730, Germany

Location

Malteser Krankenhaus St. Franziskus-Hospital

Flensburg, 24939, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Gießen

Giessen, 35392, Germany

Location

Katholisches Karl-Leisner-Klinikum gGmbH, Wilhelm-Anton-Hospital gGmbH Goch

Goch, 47574, Germany

Location

Universitätsmedizin Greifswald

Greifswald, 17475, Germany

Location

Asklepios Kliniken Hamburg GmbH St. Georg

Hamburg, 20099, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Evangelisches Krankenhaus Hamm gGmbH

Hamm, 59063, Germany

Location

Klinikum Region Hannover - Klinikum Siloah

Hanover, 30459, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

SLK-Kliniken GmbH Heilbronn

Heilbronn, 74078, Germany

Location

Marienhospital Herne, Klinikum der Ruhr

Herne, 44625, Germany

Location

Kaiserslautern, Westpfalz-Klinikum

Kaiserslautern, 67655, Germany

Location

Städtisches Klinikum Karlsruhe gGmbH

Karlsruhe, 76133, Germany

Location

Klinikum Lippe-Lemgo

Lemgo, 32657, Germany

Location

Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen, 67063, Germany

Location

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

Location

Klinikum Lüdenscheid

Lüdenscheid, 58515, Germany

Location

Universitätsklinikum Magdeburg

Magdeburg, 39120, Germany

Location

Klinikum der Johannes Gutenberg Universität

Mainz, 55131, Germany

Location

Klniikum Hochsauerland GmbH

Meschede, 59872, Germany

Location

Johannes Wesling Klinikum Minden

Minden, 32429, Germany

Location

Klinikum rechts der Isar München

München, 81675, Germany

Location

Ortenau Klinikum, Offenburg-Gengenbach

Offenburg, 77654, Germany

Location

Pius Hospital Oldenburg

Oldenburg, 26121, Germany

Location

Klinikum Oldenburg AöR

Oldenburg, 26133, Germany

Location

Klinikum Passau

Passau, 94032, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Marienhaus Klinikum St. Elisabeth Saarlouis

Saarlouis, 66740, Germany

Location

Klinikum Stuttgart

Stuttgart, 70174, Germany

Location

Stuttgart, Diakonie-Klinikum

Stuttgart, 70176, Germany

Location

Klinikum Traunstein

Traunstein, 83278, Germany

Location

Mutterhaus der Borromäerinnen

Trier, 54290, Germany

Location

Krankenhaus der Barmherzigen Brüder Trier

Trier, 54292, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Schwarzwald-Baar Klinikum Villingen- Schwenningen GmbH

Villingen-Schwenningen, 78052, Germany

Location

Helios Klinikum Wuppertal

Wuppertal, 42283, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; Daunorubicin; CPX-351

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 19, 2019
• First Posted: April 1, 2019
• Study Start: September 4, 2019
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 17, 2025

Record last verified: 2025-07

Locations

AU (6); DE (56)