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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

Tracking Information
First Submitted Date  ICMJE May 28, 2015
First Posted Date  ICMJE June 3, 2015
Last Update Posted Date February 8, 2019
Study Start Date  ICMJE June 2015
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 4, 2017)
Disease-free survival [ Time Frame: on day 56 after allogeneic SCT ]
Disease-free survival
Original Primary Outcome Measures  ICMJE
 (submitted: June 2, 2015)
Disease-free survival [ Time Frame: on day 56 after allogeneic SCT ]
Change History Complete list of historical versions of study NCT02461537 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 4, 2017)
  • Overall survival [ Time Frame: 4 weeks, 8 weeks, and 24 weeks from randomization ]
    Overall survival
  • Rate of allogeneic transplantation [ Time Frame: 4 weeks, 8 weeks, and 16 weeks from randomization ]
    Rate of allogeneic transplantation
  • Incidence of CR [ Time Frame: at 4 weeks, 8 weeks, and 24 weeks from randomization ]
    Incidence of CR
Original Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2015)
  • Overall survival [ Time Frame: 4 weeks, 8 weeks, and 24 weeks from randomization ]
  • Rate of allogeneic transplantation [ Time Frame: 4 weeks, 8 weeks, and 16 weeks from randomization ]
  • Incidence of CR [ Time Frame: at 4 weeks, 8 weeks, and 24 weeks from randomization ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Impact of Remission Induction Chemotherapy Prior to Allogeneic SCT in Relapsed and Poor-response Patients With AML
Official Title  ICMJE Evaluation of the Impact of Remission Induction Chemotherapy Prior to Allogeneic Stem Cell Transplantation in Relapsed and Poor-response Patients With AML
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia
Intervention  ICMJE
  • Drug: HAM
    High-dose cytarabine 1 - 3 g/m2 (days 1-3)/Mitoxantrone 20 mg/m2 (days3-5)
  • Drug: LDAC and/or Mitoxantrone
    Low-dose cytarabine 20 mg/m2 (days 1-10) and/ or mitoxantrone 10mg/m2 (max 3 doses)
Study Arms  ICMJE
  • Active Comparator: RIST(remission induction)
    high-dose cytarabine 3 g/m2 (days 1-3)/mitoxantrone 10mg/m2 (days 3-5)
    Intervention: Drug: HAM
  • Experimental: DISC (disease control)
    low-dose cytarabine 20 mg/ m2 and /or mitoxantrone 10mg/m2
    Intervention: Drug: LDAC and/or Mitoxantrone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 2, 2015)
308
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Raquel Palencia 49351210798 ext 21 palencia@dkms.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02461537
Other Study ID Numbers  ICMJE DKMS-14-01
2014-003124-44 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party DKMS gemeinnützige GmbH
Study Sponsor  ICMJE DKMS gemeinnützige GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Johannes Schetelig Universtitätsklinikum Dresden
PRS Account DKMS gemeinnützige GmbH
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP