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Impact of Remission Induction Chemotherapy Prior to Allogeneic SCT in Relapsed and Poor-response Patients With AML (ETAL3-ASAP)

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ClinicalTrials.gov Identifier: NCT02461537
Recruitment Status : Recruiting
First Posted : June 3, 2015
Last Update Posted : February 8, 2019
Sponsor:
Information provided by (Responsible Party):
DKMS gemeinnützige GmbH

Brief Summary:
This trial compares outcome of two treatment strategies for patients with high-risk AML who failed to achieve or maintain a complete remission with standard therapy. Patients will be randomized between two strategies. The standard strategy is aimed at achieving a complete remission by aggressive salvage chemotherapy using high dose cytarabine and mitoxantrone, . The alternative is a less toxic disease-control strategy of disease monitoring and, if necessary, low-dose cytarabine or mitoxantrone prior to allogeneic transplantation, which should be performed as soon as possible.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: HAM Drug: LDAC and/or Mitoxantrone Phase 3

Detailed Description:

Patients with high-risk acute myeloid leukemia (AML) who relapsed or showed a poor response to induction chemotherapy have a dismal prognosis. For these patients, allogeneic transplantation is the recommended treatment. While allogeneic transplantation may be considered as the ultimate treatment concept, the treatment path to transplantation is not well defined.

The traditional approach to pursue a complete remission by means of aggressive reinduction chemotherapy prior to allogeneic transplantation. This approach is associated with potentially life-threatening toxicities and has limited efficacy. As a result, only some patients will reach allogeneic transplantation in complete remission.

To reduce the number of patients who die or who are ineligible for transplantation due to the toxicity of aggressive induction chemotherapy, other bridging options have been explored. One promising alternative is to abstain from remission induction. Instead, disease control by means of less aggressive chemotherapy or simply monitoring leukemic proliferation can be considered.

This randomized trial will identify if there is non-inferiority of the less toxic approach, compared to the standard approach of remission induction by aggressive chemotherapy prior to allogeneic transplantation.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 308 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of the Impact of Remission Induction Chemotherapy Prior to Allogeneic Stem Cell Transplantation in Relapsed and Poor-response Patients With AML
Study Start Date : June 2015
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : May 2022


Arm Intervention/treatment
Active Comparator: RIST(remission induction)
high-dose cytarabine 3 g/m2 (days 1-3)/mitoxantrone 10mg/m2 (days 3-5)
Drug: HAM
High-dose cytarabine 1 - 3 g/m2 (days 1-3)/Mitoxantrone 20 mg/m2 (days3-5)

Experimental: DISC (disease control)
low-dose cytarabine 20 mg/ m2 and /or mitoxantrone 10mg/m2
Drug: LDAC and/or Mitoxantrone
Low-dose cytarabine 20 mg/m2 (days 1-10) and/ or mitoxantrone 10mg/m2 (max 3 doses)




Primary Outcome Measures :
  1. Disease-free survival [ Time Frame: on day 56 after allogeneic SCT ]
    Disease-free survival


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 4 weeks, 8 weeks, and 24 weeks from randomization ]
    Overall survival

  2. Rate of allogeneic transplantation [ Time Frame: 4 weeks, 8 weeks, and 16 weeks from randomization ]
    Rate of allogeneic transplantation

  3. Incidence of CR [ Time Frame: at 4 weeks, 8 weeks, and 24 weeks from randomization ]
    Incidence of CR



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Signed written informed consent.
  • Male and female patients of 18 to 75 years of age.
  • Diagnosis of AML according to WHO criteria.
  • Patient is fit for aggressive induction chemotherapy and transplantation by assessment of an experienced hematologist.
  • No history of chronic pulmonary disease and absence of dyspnea. Otherwise, documented diffusion lung capacity for carbon monoxide ( DLCO ) ≤ 40 percent ( adjusted for hemoglobin, if available ) and FEV1 / FVC ≥ 50 percent.
  • HLA - identical sibling. or
  • HLA - compatible unrelated donor ( ≥ 9 /10 antigens matched for HLA - A, - B, - C, -DRB 1, and - DQB 1 ) with completed confirmatory typing or
  • Two unrelated donors with > 90 percent probability of a 9 /10 match for HLA - A, - B, - C, - DRB 1, and - DRQB 1, according to Opti Match ® list.

For the relapse stratum

  • First AML relapse, defined as ≥ 5 percent bone marrow blasts and / or extramedullary AML manifestation.

For the poor - responders stratum

  • AML that evolves from previously documented myelodysplastic syndrome ( MDS ),

and / or

  • diagnosis of therapy-related myeloid neoplasm ( t - MN ), and / or

a ) If patient ≤ 60 years old adverse risk AML according to ELN - criteria and ≥ 5 percent bone marrow blasts after the first cycle of induction therapy.

b ) If patient > 60 years old non-favourable risk AML according to ELN - criteria and ≥ 5 percent bone marrow blasts after the first cycle of induction therapy.

Exclusion Criteria

  • Acute promyelocytic leukemia ( APL ).
  • WBC count of ≥ 50 GPt / L at study inclusion.
  • For patients in the poor - responder stratum the first cycle of induction therapy must not contain HDAC, defined as cytarabine at single-doses of > 1 g / m 2.
  • Patient has received more than 440 mg / m2 daunorubicin equivalents.
  • Severe organ dysfunction, defined as
  • Left ventricular ejection fraction < 50 percent.
  • Patients who receive supplementary continuous oxygen.
  • Serum bilirubin > 1.5 x ULN ( if not considered Gilbert-Syndrome ), ASAT / ALAT > 5 x ULN.
  • Estimated GFR < 50 ml / min.
  • Treatment with any investigational drug within 10 days before study entry.
  • Uncontrolled infection at the time of enrollment.
  • History of allogeneic transplantation.
  • Manifestation of AML in the central nervous system.
  • Pregnant or breast - feeding women.
  • Men unable or unwilling to use adequate contraception methods from start of study treatment to minimum of six months after the last dose of chemotherapy.
  • Women of childbearing potential except those who fulfill the following criteria: Post-menopausal or post-operative or continuous and correct application of a contraception method with a Pearl Index < 1 percent or sexual abstinence or vasectomy of the sexual partner.

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): NCT02461537


Contacts
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Contact: Raquel Palencia 49351210798 ext 21 palencia@dkms.de

Locations
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Germany
Universitätsmedizin Mannheim III. Medizinische Klinik Hämatologie und Onkologie Recruiting
Mannheim, Baden-Württemberg, Germany, 68167
Contact: Michaela Hausmann         
Principal Investigator: Stefan A. Klein, PD Dr med         
Robert-Bosch-Krankenhaus Recruiting
Stuttgart, Baden-Württemberg, Germany, 70376
Contact: Sandra Heidmann         
Principal Investigator: Martin Kaufmann, Dr. med.         
Universitätsklinikum Tübingen Medizinische Klinik und Poliklinik Onkologie, Hämatologie, Rheumatologie und Pulmologie Recruiting
Tübingen, Baden-Württemberg, Germany, 72076
Contact: Anja Junker         
Principal Investigator: Wolfgang Bethge, Prof Dr Med         
Rems-Murr-Kliniken gGmbH Recruiting
Winnenden, Baden-Württemberg, Germany, 71364
Contact: Kathrin Kühn    07195591 ext 36022    kathrin.kuehn@rems-murr-klinikemn.de   
Principal Investigator: Markus Schaich, Prof.Dr.med.         
Klinikum Augsburg Recruiting
Augsburg, Bavaria, Germany, 86156
Contact: Franziska Knieler         
Contact: Silvia Söllner         
Principal Investigator: Christoph Schmid, PD Dr. med.         
Universitätsklinikum Erlangen Recruiting
Erlangen, Bavaria, Germany, 91054
Contact: Ulrike Höfer         
Contact: Evi Weiß         
Principal Investigator: Stefan Krause, Prof Dr med         
Klinikum Nürnberg Nord Medizinische Klinik 5 Recruiting
Nürnberg, Bavaria, Germany, 90419
Contact: Karin Westphal         
Principal Investigator: Kerstin Schäfer-Eckart, Dr Med         
University Hospital Recruiting
Dresden, Free State Of Saxony, Germany, 01307
Contact: Johannes Schetelig, Prof         
Elblandkliniken Stiftung & Co. KG Recruiting
Riesa, Free State Of Saxony, Germany, 01589
Contact: Maria Sonnenfeld    0352575 ext 3075    maria.sonnenfeld@elblandkliniken.de   
Principal Investigator: Jörg Schubert, Prof.Dr.med.         
Universitätsklinikum Frankfurt, Med. Klinik II - Hämatologie/Onkologie Recruiting
Frankfurt am Main, Hessen, Germany, 60595
Contact: Wagner-Scherneck         
Principal Investigator: Gesine Bug, PD Dr. med.         
Universitätsklinikum Aachen, AÖR Recruiting
Aachen, Nordrhein-Westphalen, Germany, 52074
Contact: Carmen Döring    024180 ext 35168    cdoering@ukaachen.de   
Principal Investigator: Edgar Jost, PD Dr. med.         
Universitätsklinikum Essen (AöR) Not yet recruiting
Essen, Nordrhein-Westphalen, Germany, 45147
Contact: Elke Günther    0201723 ext 1861      
Principal Investigator: Richard Noppeney, Dr.med.         
Universitätsklinikum Münster, KMT-Zentrum Recruiting
Münster, North Rhine-Westphalia, Germany, 48149
Contact: Vera Gordon         
Contact: Birgit Mayerhoffer         
Principal Investigator: Matthias Stelljes, Prof Dr Med         
III. Medizinische Klinik und Poliklinik Universitätsmedizin der Johannes Gutenberg-Universität Mainz Recruiting
Mainz, Rhineland-Palatinate, Germany, 55131
Contact: Christiane Schön         
Contact: Andrea Schulz         
Principal Investigator: Eva Wagner, Dr Med         
Universitätsklinikum Halle (Saale) Klinik für Innere Medizin IV Hämatologie/Onkologie/Hämostaseologie Recruiting
Halle, Saxony-Anhalt, Germany, 06120
Contact: Antje Kleinbauer         
Principal Investigator: Lutz Peter Müller, Dr med habil         
Helios Klinikum Berlin Buch Not yet recruiting
Berlin, Germany, 13125
Contact: Katrin Müller    0309401 ext 52189      
Principal Investigator: Herrad Baurmann, Dr.med.         
Sponsors and Collaborators
DKMS gemeinnützige GmbH
Investigators
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Study Chair: Johannes Schetelig Universtitätsklinikum Dresden

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Responsible Party: DKMS gemeinnützige GmbH
ClinicalTrials.gov Identifier: NCT02461537     History of Changes
Other Study ID Numbers: DKMS-14-01
2014-003124-44 ( EudraCT Number )
First Posted: June 3, 2015    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
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Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Mitoxantrone
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors