Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy With CPX-351 in Adult Patients With Newly Diagnosed AML and Intermediate- or Adverse Genetics
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03897127 |
Recruitment Status :
Recruiting
First Posted : April 1, 2019
Last Update Posted : September 10, 2019
|
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Acute Myeloid Leukemia | Drug: Cytarabine Drug: Daunorubicin Drug: CPX-351 | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 593 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | September 4, 2019 |
Estimated Primary Completion Date : | June 2023 |
Estimated Study Completion Date : | June 2023 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Standard arm |
Drug: Cytarabine
Induction therapy: 200 mg/m2 i.v. (continuously) d1-7 Consolidation therapy:
Drug: Daunorubicin Induction therapy: 60 mg/m2 i.v. (1 hr) d1-3 |
Experimental: Investigational arm |
Drug: CPX-351
Induction 1:
Induction 2: • Patients age 18-60 years
Consolidation therapy: o CPX-351 29 mg/m2 daunorubicin / 65 mg/m2 cytarabine [65 U/m²] i.v. (90 min) d1,3 |
- Event-free survival (EFS) [ Time Frame: 2 years ]
- Overall survival (OS) [ Time Frame: 2 years ]
- Relapse-free survival (RFS) [ Time Frame: 2 years ]
- Cumulative incidence of relapse (CIR) [ Time Frame: 2 years ]
- Cumulative incidence of death (CID) [ Time Frame: 2 years ]
- Rate of objective response [ Time Frame: 2 months ]complete remission [CR], CR with incomplete hematologic recovery [CRi], CR without minimal residual disease [CRMRD-]
- Adverse events [ Time Frame: 8 months ]Incidence and intensity of adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) version v5.0
- Analysis of rate of response according to cytogenetic and molecular genetic changes [ Time Frame: 2 years ]Exploratory endpoint
- Analysis of Overall survival according to cytogenetic and molecular genetic changes [ Time Frame: 2 years ]Exploratory endpoint
- Analysis of Relapse-free survival according to cytogenetic and molecular genetic changes [ Time Frame: 2 years ]Exploratory endpoint
- Analysis of Event-free survival according to cytogenetic and molecular genetic changes [ Time Frame: 2 years ]Exploratory endpoint
- Analysis of Overall Survival according to Minimal Residual Disease results during and after treatment [ Time Frame: 2 years ]Exploratory endpoint
- Analysis of Event-free Survival according to Minimal Residual Disease results during and after treatment [ Time Frame: 2 years ]Exploratory endpoint
- QoL NCI PRO-CTCAE (National Cancer Institute) Patient Reported Outcomes Common Terminology Criteria for Adverse Events questionnaire) [ Time Frame: 2 years ]PRO-CTCAE responses are scored from 0 to 4, whereas lower values represent a better outcome. For this trial, the burden of symptoms that will be captured by this questionnaire comprises nausea, diarrhea, rash, and alopecia.
- QoL EORTC QLQ-FA12 [ Time Frame: 2 years ]The EORTC QLQ-FA12 module complements the core EORTC QLQ-C30 questionnaire regarding fatigue. . Each item can be scored in four dimension on a scale from 1 to 4 with higher scores indicating worse symptoms.
- QoL EORTC QLQ-C30 (Core Quality of Life Questionnaire developed by European Organization for Research and Treatment of Cancer ) [ Time Frame: 2 years ]The EORTC QLQ-C30 subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher scores on symptom scales indicating worse symptoms.
- Rate of hospitalization including admissions at intensive care unit (ICU) [ Time Frame: 8 months ]Exploratory endpoint
- Reasons for hospitalization [ Time Frame: 8 months ]Exploratory endpoint
- days of hospitalization by treatment setting [ Time Frame: 8 months ]Exploratory endpoint
- rate of use of anti-infectives and other medications, e.g. against nausea or vomiting [ Time Frame: 8 months ]Exploratory endpoint
- additional therapies administered [ Time Frame: 8 months ]Exploratory endpoint
- place of chemotherapy administration (inpatient vs outpatient setting) [ Time Frame: 8 months ]Exploratory endpoint
- duration of administration [ Time Frame: 8 months ]Exploratory endpoint
- number of outpatient visits [ Time Frame: 8 months ]Exploratory endpoint
- Frequency of salvage therapies [ Time Frame: 8 months ]Exploratory endpoint

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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 (for younger patients [18-60 years of age] ≤ 1)
- 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 Trial Coordinator
- 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 Trial Coordinator
- No prior chemotherapy for acute leukemia 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 >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 6 months after the last dose of CPX-351
- 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 6 months after the last dose of CPX-351. 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 CPX-351). 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)
Exclusion Criteria:
-
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
- 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
- Known history of positive test for hepatitis B surface Antigen (HBSAg) or hepatitis C antibody or history of positive test for Human Immunodeficiency Virus (HIV)
-
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:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer
- Severe neurological or psychiatric disorder interfering with ability to give an informed consent
- 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
- No consent for biobanking of patient's biological specimens
- 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
- 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.
- Known or suspected hypersensitivity to cytarabine, daunorubicin or liposomal products and/or any excipients
- History of Wilson's disease or other copper-metabolism disorder
- Receipt of live, attenuated vaccine within 30 days prior to the study inclusion (NOTE: Subjects, if enrolled, should not receive live vaccine during the study and until 6 months after the therapy).

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03897127
Contact: Peter Paschka, MD | 0049-731-500 ext 45521 | peter.paschka@uniklinik-ulm.de |
Germany | |
Klinikum Aschaffenburg | Not yet recruiting |
Aschaffenburg, Germany, 63739 | |
Contact: Manfred Welslau, MD | |
Contact: Simone Liebler, MD | |
Vivantes Klinikum Am Urban | Not yet recruiting |
Berlin, Germany, 10967 | |
Contact: Christian Scholz, MD | |
Contact: Annette Dieing, MD | |
Vivantes Klinikum Neukölln | Not yet recruiting |
Berlin, Germany, 12351 | |
Contact: Maike de Witt, MD | |
Contact: Lore Marretta, MD | |
Charité Berlin ‐ Campus Virchow‐Klinikum | Not yet recruiting |
Berlin, Germany, 13353 | |
Contact: Jörg Westermann, MD | |
Contact: Anne Flörcken, MD | |
Knappschaftskrankenhaus Bochum‐Langendreer | Not yet recruiting |
Bochum, Germany, 44892 | |
Contact: Roland Schroers, MD | |
Contact: Alexander Baraniskin, MD | |
Universitätsklinikum Bonn | Not yet recruiting |
Bonn, Germany, 53105 | |
Contact: Georg Feldmann, MD | |
Contact: Juliane Klein, MD | |
Städtisches Klinikum Braunschweig gGmbH | Not yet recruiting |
Braunschweig, Germany, 38114 | |
Contact: Jürgen Krauter, MD | |
Contact: Arne Trummer, MD | |
Klinikum Bremen‐Mitte | Not yet recruiting |
Bremen, Germany, 28177 | |
Contact: Bernd Hertenstein, MD | |
Contact: Stephan Kaun, MD | |
Klinikum Darmstadt | Not yet recruiting |
Darmstadt, Germany, 64283 | |
Contact: Helga Bernhard, MD | |
Contact: Stephan Schäfer, MD | |
St.‐Johannes‐Hospital | Not yet recruiting |
Dortmund, Germany, 44137 | |
Contact: Darina Kodzhabasheva, MD | |
Contact: Ralf Georg Meyer, MD | |
Universitätsklinikum Düsseldorf | Not yet recruiting |
Düsseldorf, Germany, 40225 | |
Contact: Thomas Schroeder, MD | |
Contact: Ulrich Germing, MD | |
Kliniken Essen Süd, Ev. Krankenhaus Essen‐ Werden gGmbH | Not yet recruiting |
Essen, Germany, 45239 | |
Contact: Mohammed Wattad, MD | |
Contact: Peter Reimer, MD | |
Klinikum Esslingen | Not yet recruiting |
Esslingen, Germany, 73730 | |
Contact: Swen Wessendorf, MD | |
Contact: Rebekka Mannal, MD | |
Malteser Krankenhaus St. Franziskus‐Hospital | Not yet recruiting |
Flensburg, Germany, 24939 | |
Contact: Nadezda Basara, MD | |
Contact: Helge Menzel, MD | |
Universitätsklinikum Gießen | Not yet recruiting |
Gießen, Germany, 35392 | |
Contact: Matthias Rummel, MD | |
Contact: Alexander Burchardt, MD | |
Katholisches Karl‐Leisner‐Klinikum gGmbH, Wilhelm‐Anton‐Hospital gGmbH Goch | Not yet recruiting |
Goch, Germany, 47574 | |
Contact: Volker Runde, MD | |
Contact: Jörn Westheider, MD | |
Universitätsklinikum Hamburg‐Eppendorf | Not yet recruiting |
Hamburg, Germany, 20246 | |
Contact: Walter Fiedler, MD | |
Contact: Melanie Janning, MD | |
Asklepios Klinik Altona | Not yet recruiting |
Hamburg, Germany, 22763 | |
Contact: Hans Salwender, MD | |
Contact: Cord Beeger, MD | |
Evangelisches Krankenhaus Hamm gGmbH | Not yet recruiting |
Hamm, Germany, 59063 | |
Contact: Elisabeth Lange, MD | |
Contact: Thomas Wehler, MD | |
Sub-Investigator: Andrea Stoltefuß, MD | |
Klinikum Region Hannover ‐ Klinikum Siloah | Not yet recruiting |
Hannover, Germany, 30459 | |
Contact: Martin Müller, MD | |
Contact: Kim Marienhagen, MD | |
Sub-Investigator: Daniela Dörfel, MD | |
Medizinische Hochschule Hannover | Not yet recruiting |
Hannover, Germany, 30625 | |
Contact: Felicitas Thol, MD | |
Contact: Michael Heuser, MD | |
Westküstenklinikum Heide | Not yet recruiting |
Heide, Germany, 25746 | |
Contact: Karen Rußwurm, MD | |
Contact: Georg Rußwurm, MD | |
SLK‐Kliniken GmbH Heilbronn | Not yet recruiting |
Heilbronn, Germany, 74078 | |
Contact: Markus Lindauer, MD | |
Contact: Uwe Martens, MD | |
Marienhospital Herne, Klinikum der Ruhr | Not yet recruiting |
Herne, Germany, 44625 | |
Contact: Beate Schultheis, MD | |
Contact: Dirk Strumberg, MD | |
Kaiserslautern, Westpfalz‐Klinikum | Not yet recruiting |
Kaiserslautern, Germany, 67655 | |
Contact: Gerhard Held, MD | |
Contact: Milena Pfeifer, MD | |
Städtisches Klinikum Karlsruhe gGmbH | Not yet recruiting |
Karlsruhe, Germany, 76133 | |
Contact: Mark Ringhoffer, MD | |
Contact: Lukas Kündgen, MD | |
Caritas‐Krankenhaus Lebach | Not yet recruiting |
Lebach, Germany, 66822 | |
Contact: Stephan Kremers, MD | |
Contact: Gero Leonhard-Helmschmidt, MD | |
Klinikum Lippe‐Lemgo | Not yet recruiting |
Lemgo, Germany, 32657 | |
Contact: Hesse Tanja, MD | |
Contact: Frank Hartmann, MD | |
Klinikum Lüdenscheid | Not yet recruiting |
Lüdenscheid, Germany, 58515 | |
Contact: Gerhard Heil, MD | |
Contact: Christiane Maria Hempel-Overhage, MD | |
Universitätsklinikum Magdeburg | Not yet recruiting |
Magdeburg, Germany, 39120 | |
Contact: Martin Mikusko, MD | |
Contact: Vanja Zeremski, MD | |
Klinikum der Johannes Gutenberg Universität | Not yet recruiting |
Mainz, Germany, 55131 | |
Contact: Michael Kühn, MD | |
Contact: Markus Radsak, MD | |
Johannes Wesling Klinikum Minden | Not yet recruiting |
Minden, Germany, 32429 | |
Contact: Hans Joachim Tischler, MD | |
Contact: Kai Wille, MD | |
Klinikum rechts der Isar München | Not yet recruiting |
München, Germany, 81675 | |
Contact: Katharina Götze, MD | |
Contact: Isabella Miller, MD | |
Ortenau Klinikum, Offenburg‐Gengenbach | Not yet recruiting |
Offenburg, Germany, 77654 | |
Contact: Carsten Schwänen, MD | |
Contact: Irmgard Dresel, MD | |
Sub-Investigator: Jochen Reutschel, MD | |
Pius Hospital Oldenburg | Not yet recruiting |
Oldenburg, Germany, 26121 | |
Contact: Imme Conradi, MD | |
Contact: Frank Griesinger, MD | |
Klinikum Passau | Not yet recruiting |
Passau, Germany, 94032 | |
Contact: Thomas Südhoff, MD | |
Contact: Thorsten Nitsch, MD | |
Universitätsklinikum Regensburg | Not yet recruiting |
Regensburg, Germany, 93053 | |
Contact: Daniel Heudobler, MD | |
Contact: Simone Thomas, MD | |
Klinikum Stuttgart | Not yet recruiting |
Stuttgart, Germany, 70174 | |
Contact: Jan Schleicher, MD | |
Contact: Alf Jörg Zerzweck, MD | |
Marienhospital Stuttgart | Not yet recruiting |
Stuttgart, Germany, 70199 | |
Contact: Claudio Denzlinger, MD | |
Contact: Lale Kaylkci, MD | |
Klinikum Traunstein | Not yet recruiting |
Traunstein, Germany, 83278 | |
Contact: Elisabeth Dietl, MD | |
Contact: Thomas Kubin, MD | |
Mutterhaus der Borromäerinnen | Not yet recruiting |
Trier, Germany, 54290 | |
Contact: Rolf Mahlberg, MD | |
Contact: Stefan Hebel, MD | |
Krankenhaus der Barmherzigen Brüder Trier | Not yet recruiting |
Trier, Germany, 54292 | |
Contact: Heinz Kirchen, MD | |
Contact: Monika Lankeshofer-Loch, MD | |
Universitätsklinikum Tübingen | Not yet recruiting |
Tübingen, Germany, 72076 | |
Contact: Marcus Schittenhelm, MD | |
Contact: Dominik Schneidawind, MD | |
Universitätsklinikum Ulm | Recruiting |
Ulm, Germany, 89081 | |
Contact: Peter Paschka, MD | |
Contact: Verena Gaidzik, MD | |
Schwarzwald‐Baar Klinikum Villingen‐ Schwenningen GmbH | Not yet recruiting |
Villingen-Schwenningen, Germany, 78052 | |
Contact: Paul Graf La Rosée, MD | |
Contact: Martin Henkes, MD | |
Helios Klinikum Wuppertal | Not yet recruiting |
Wuppertal, Germany, 42283 | |
Contact: Silke Schostock, MD | |
Contact: Blasius Liss, MD |
Responsible Party: | Peter Paschka, Principal Investigator, University of Ulm |
ClinicalTrials.gov Identifier: | NCT03897127 History of Changes |
Other Study ID Numbers: |
AMLSG 30-18 |
First Posted: | April 1, 2019 Key Record Dates |
Last Update Posted: | September 10, 2019 |
Last Verified: | September 2019 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
CPX-351 Acute Myeloid Leukemia |
Leukemia, Myeloid Leukemia, Myeloid, Acute Leukemia Neoplasms by Histologic Type Neoplasms Cytarabine Daunorubicin Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action |
Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors |