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

NCT02461537 | Completed Phase 3

• 2 other identifiers: DKMS-14-012014-003124-44
• Study Type: interventional
• Target: 281
• Locations: 1 country
• Sites: 18

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

  Disease-free survival

  on day 56 after allogeneic SCT

Secondary Outcomes (3)

• Overall survival

  4 weeks, 8 weeks, and 24 weeks from randomization

• Rate of allogeneic transplantation

  4 weeks, 8 weeks, and 16 weeks from randomization

• Incidence of CR

  at 4 weeks, 8 weeks, and 24 weeks from randomization

Study Arms (2)

RIST(remission induction)

ACTIVE COMPARATOR

high-dose cytarabine 3 g/m2 (days 1-3)/mitoxantrone 10mg/m2 (days 3-5)

Drug: HAM

DISC (disease control)

EXPERIMENTAL

low-dose cytarabine 20 mg/ m2 and /or mitoxantrone 10mg/m2

Drug: LDAC and/or Mitoxantrone

Interventions

HAM DRUG

High-dose cytarabine 1 - 3 g/m2 (days 1-3)/Mitoxantrone 20 mg/m2 (days3-5)

RIST(remission induction)

LDAC and/or Mitoxantrone DRUG

Low-dose cytarabine 20 mg/m2 (days 1-10) and/ or mitoxantrone 10mg/m2 (max 3 doses)

DISC (disease control)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Acute promyelocytic leukemia ( APL ).
• 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.

Sponsors & Collaborators

• DKMS gemeinnützige GmbH: lead

Study Sites (18)

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitätsmedizin Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

Location

Robert-Bosch-Krankenhaus

Stuttgart, Baden-Wurttemberg, 70376, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Rems-Murr-Kliniken gGmbH

Winnenden, Baden-Wurttemberg, 71364, Germany

Location

Klinikum Augsburg

Augsburg, Bavaria, 86156, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Klinikum Nürnberg Nord

Nuremberg, Bavaria, 90419, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, 60595, Germany

Location

Universitätsklinikum Aachen, AÖR

Aachen, Nordrhein-Westphalen, 52074, Germany

Location

Universitätsklinikum Essen (AöR)

Essen, Nordrhein-Westphalen, 45147, Germany

Location

Universitätsklinikum Münster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

University Hospital

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

Location

Elblandkliniken Stiftung & Co. KG

Riesa, Saxony, 01589, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, Saxony-Anhalt, 06120, Germany

Location

Helios Klinikum Berlin Buch

Berlin, 13125, Germany

Location

Related Publications (2)

• Stelljes M, Middeke JM, Bug G, Wagner-Drouet EM, Muller LP, Schmid C, Krause SW, Bethge W, Jost E, Platzbecker U, Klein SA, Niederland J, Kaufmann M, Schafer-Eckart K, Baldauf H, Stolzel F, Trost S, Rollig C, von Bonin M, Egger-Heidrich K, Kunadt D, Steffen B, Hauptrock B, Schliemann C, Sockel K, Lang F, Kriege O, Schaffrath J, Reicherts C, Berdel WE, Serve H, Ehninger G, Schmidt AH, Mikesch JH, Bornhauser M, Schetelig J. Disease risk but not remission status determines transplant outcomes in AML: long-term outcomes of the ASAP trial. Blood. 2025 Nov 6;146(19):2293-2305. doi: 10.1182/blood.2025028730.

  PMID: 40737595 DERIVED

• Stelljes M, Middeke JM, Bug G, Wagner-Drouet EM, Muller LP, Schmid C, Krause SW, Bethge W, Jost E, Platzbecker U, Klein SA, Schubert J, Niederland J, Kaufmann M, Schafer-Eckart K, Schaich M, Baldauf H, Stolzel F, Petzold C, Rollig C, Alakel N, Steffen B, Hauptrock B, Schliemann C, Sockel K, Lang F, Kriege O, Schaffrath J, Reicherts C, Berdel WE, Serve H, Ehninger G, Schmidt AH, Bornhauser M, Mikesch JH, Schetelig J; Study Alliance Leukemia and the German Cooperative Transplant Study Group. Remission induction versus immediate allogeneic haematopoietic stem cell transplantation for patients with relapsed or poor responsive acute myeloid leukaemia (ASAP): a randomised, open-label, phase 3, non-inferiority trial. Lancet Haematol. 2024 May;11(5):e324-e335. doi: 10.1016/S2352-3026(24)00065-6. Epub 2024 Apr 4.

  PMID: 38583455 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Study Officials

• Johannes Schetelig, Prof Dr med

  Universtitätsklinikum Dresden

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2015
• First Posted: June 3, 2015
• Study Start: September 17, 2015
• Primary Completion: April 5, 2022
• Study Completion: January 12, 2024
• Last Updated: January 19, 2024

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (18)