Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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
Sponsor:
Collaborator:
Jazz Pharmaceuticals
Information provided by (Responsible Party):
Peter Paschka, University of Ulm

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. Event-free survival (EFS) will be the primary endpoint as defined by standard criteria (Döhner 2017).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Cytarabine Drug: Daunorubicin Drug: CPX-351 Phase 3

Layout table for study information
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:

  • 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

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

Experimental: Investigational arm Drug: CPX-351

Induction 1:

  • Patients age 18-60 years

    o CPX-351 55 mg/m2 daunorubicin / 125 mg/m2 cytarabine [125 U/m²] i.v. (90 min) d1,3,5

  • Patients age >60 years o CPX-351 44 mg/m2 daunorubicin / 100 mg/m2 cytarabine [100 U/m²] i.v. (90 min) d1,3,5

Induction 2:

• Patients age 18-60 years

  • CPX-351 55 mg/m2 daunorubicin / 125 mg/m2 cytarabine [125 U/m²] i.v. (90 min) d1,3

    • Patients age >60 years

  • 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





Primary Outcome Measures :
  1. Event-free survival (EFS) [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 2 years ]
  2. Relapse-free survival (RFS) [ Time Frame: 2 years ]
  3. Cumulative incidence of relapse (CIR) [ Time Frame: 2 years ]
  4. Cumulative incidence of death (CID) [ Time Frame: 2 years ]
  5. Rate of objective response [ Time Frame: 2 months ]
    complete remission [CR], CR with incomplete hematologic recovery [CRi], CR without minimal residual disease [CRMRD-]

  6. 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


Other Outcome Measures:
  1. Analysis of rate of response according to cytogenetic and molecular genetic changes [ Time Frame: 2 years ]
    Exploratory endpoint

  2. Analysis of Overall survival according to cytogenetic and molecular genetic changes [ Time Frame: 2 years ]
    Exploratory endpoint

  3. Analysis of Relapse-free survival according to cytogenetic and molecular genetic changes [ Time Frame: 2 years ]
    Exploratory endpoint

  4. Analysis of Event-free survival according to cytogenetic and molecular genetic changes [ Time Frame: 2 years ]
    Exploratory endpoint

  5. Analysis of Overall Survival according to Minimal Residual Disease results during and after treatment [ Time Frame: 2 years ]
    Exploratory endpoint

  6. Analysis of Event-free Survival according to Minimal Residual Disease results during and after treatment [ Time Frame: 2 years ]
    Exploratory endpoint

  7. 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.

  8. 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.

  9. 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.

  10. Rate of hospitalization including admissions at intensive care unit (ICU) [ Time Frame: 8 months ]
    Exploratory endpoint

  11. Reasons for hospitalization [ Time Frame: 8 months ]
    Exploratory endpoint

  12. days of hospitalization by treatment setting [ Time Frame: 8 months ]
    Exploratory endpoint

  13. rate of use of anti-infectives and other medications, e.g. against nausea or vomiting [ Time Frame: 8 months ]
    Exploratory endpoint

  14. additional therapies administered [ Time Frame: 8 months ]
    Exploratory endpoint

  15. place of chemotherapy administration (inpatient vs outpatient setting) [ Time Frame: 8 months ]
    Exploratory endpoint

  16. duration of administration [ Time Frame: 8 months ]
    Exploratory endpoint

  17. number of outpatient visits [ Time Frame: 8 months ]
    Exploratory endpoint

  18. Frequency of salvage therapies [ Time Frame: 8 months ]
    Exploratory endpoint



Information from the National Library of Medicine

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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  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 (for younger patients [18-60 years of age] ≤ 1)
  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:

    • 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
  8. 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
  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 6 months after the last dose of CPX-351
  11. 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
  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 CPX-351). 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)

Exclusion Criteria:

  1. 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
  2. Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PML-RARA; or one of the other pathognomonic variant chromosomal translocations/ fusion genes
  3. AML with BCR-ABL1
  4. Prior treatment of myelodysplastic syndrome (MDS) with intensive chemotherapy or bone marrow transplant with a curative intent
  5. 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
  6. Severe obstructive or restrictive ventilation disorder
  7. Uncontrolled infection
  8. 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
  9. 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)
  10. 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
  11. Severe neurological or psychiatric disorder interfering with ability to give an informed consent
  12. 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
  13. No consent for biobanking of patient's biological specimens
  14. 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
  15. 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.
  16. Known or suspected hypersensitivity to cytarabine, daunorubicin or liposomal products and/or any excipients
  17. History of Wilson's disease or other copper-metabolism disorder
  18. 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).

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Peter Paschka, MD 0049-731-500 ext 45521 peter.paschka@uniklinik-ulm.de

Locations
Layout table for location information
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         
Sponsors and Collaborators
University of Ulm
Jazz Pharmaceuticals

Layout table for additonal information
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Peter Paschka, University of Ulm:
CPX-351
Acute Myeloid Leukemia
Additional relevant MeSH terms:
Layout table for MeSH terms
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