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NCT Number: NCT06643195

Immediate Allogeneic Hematopoietic Stem Cell Transplantation Versus Re-treatment for Patients With High-Risk Acute Myeloid Leukemia

This study aims to investigate whether immediate HSCT for patients with high-risk AML and intermediate-risk AML who have not achieved complete remission (CR) after their first induction therapy is non-inferior to re-treatment with chemotherapy.

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Key information

Conditions

AML

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Hebei Medical University Second Hospital, Shijiazhuang, Hebeisheng, China

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About this study

  • Disease control group: patients proceeded to allogeneic HSCT as soon as possible. Patients were allowed to receive low-dose chemotherapy that is not intended for the purpose of achieving a second remission.
  • Retreatment group: Receive a second course of anti-leukemic treatment prior to allogeneic HSCT. The anti-leukemic treatment regimen will be determined based on the genetic mutation status. Patients without targetable mutations will receive a combination of BCL-2 inhibitors and demethylating agents as salvage chemotherapy. Patients with targetable mutations will receive appropriate targeted therapy (e.g., FLT3 inhibitors, IDH inhibitors).

For patients who have already received targeted therapy during induction treatment, the researchers may choose the treatment regimen based on the individual patient's condition.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • AML patients aged ≥ 18 years.
  • High-risk AML patients according to the 2022 ELN standards who received one cycle of induction therapy.
  • Requires allogeneic hematopoietic stem cell transplantation (including HLA-matched or mismatched allogeneic HSCT and unrelated donor transplant).
  • KPS score greater than 60.
  • Informed consent must be signed before the start of the study procedures; if it is detrimental to the patient's condition for them to sign, the consent may be signed by a legal guardian or immediate family member.

Exclusion criteria

  • Acute promyelocytic leukemia.
  • Patient has received more than 440 mg/m2 daunorubicin equivalents. The cumulative dose is calculated by summing up isotoxic daunorubicin-equivalents for daunorubicin, doxorubicin, epirubicin, idarubicin and mitoxantrone. The conversion factors are derived from the comparison of the respective maximum doses. The conversion factor is 1 for daunorubicin, 1 for doxorubicin, 0.6 for epirubicin, 4.6 for idarubicin, and 2.7 for mitoxantrone (see worksheet for calculation).
  • Severe organ dysfunction, defined as:
  • Left ventricular ejection fraction <50%. 2) Patients who receive supplementary continuous oxygen. 3) Serum bilirubin >1.5 x ULN (if not considered Gilbert-Syndrome) or ASAT/ALAT >5 x ULN.
  • Estimated Glomerular Filtration Rate (GFR) < 50 ml/min, where: Estimated GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.203 x (0.742 if patient is female) x (1.212 if patient is black) 4. History of allogeneic transplantation. 5. Manifestation of AML in the Central Nervous System. 6. Pregnant or breastfeeding women.

Treatment and study plan

ImmediateAllogeneic Hematopoietic Stem Cell Transplantation

Other

patients proceeded to allogeneic HSCT as soon as possible. Patients were allowed to receive low-dose chemotherapy that is not intended for the purpose of achieving a second remission.

Retreatment

Other

Receive a second course of anti-leukemic treatment prior to allogeneic HSCT. The anti-leukemic treatment regimen will be determined based on the genetic mutation status. Patients without targetable mutations will receive a combination of BCL-2 inhibitors and demethylating agents as salvage chemotherapy. Patients with targetable mutations will receive appropriate targeted therapy (e.g., FLT3 inhibitors, IDH inhibitors).

Primary outcomes

  1. treatment success

    Time frame: day 56 after allogeneic HCT

    The primary endpoint, treatment success defined as complete remission on day 56 after allogeneic HCT, was defined as dichotomous success rate.

Secondary outcomes

  1. Cumulative Incidences of Allogeneic HSCT

    Time frame: HSCT rates at 4,8,16, and 24 weeks

    • Starting point: Randomization
    • Event: allogeneic HCT
    • Competing events: death, withdrawal
  2. Incidence of Complete Remission from Randomisation

    Time frame: Date of first documented CR or CRi or CRchim Death before CR/CRi/CRchim not achieve a CR or CRi by six months

    • Starting point: randomization
    • Event: Date of first documented CR or CRi or CRchim
    • Competing Event: Death before CR/CRi/CRchim
    • Administrative Censoring: not achieve a CR or CRi by six months

    b) Starting point: day 56 c) Events: Relapse (both, hematologic or molecular) and death

  3. Overall survival after HCT

    Time frame: Death

    • Starting point: HCT
    • Event: Death
  4. Event-free survival after HCT

    Time frame: death before relapse, relapse (both, hematological or molecular), and failure to achieve a CR at final remission assessment

    • Starting point: HCT
    • Events: death before relapse, relapse (both, hematological or molecular), and failure to achieve a CR at final remission assessment
  5. Leukemia-free survival from day 56 after alloHCT for patients who met the primary endpoint

    Time frame: day 56

    efined only for per-protocol treated patients who met the primary endpoint b) Starting point: day 56 c) Events: Relapse (both, hematologic or molecular) and death

  6. Rate of MRD Negative from Day 56 after HSCT

    Time frame: day 56

    • defined only for per-protocol treated patients who met the primary endpoint
    • Starting point: day 56
    • Events: MRD Negative (including MPFC, qPCR and NGS) and death
  7. 7. Overall Survival from Randomization: Measured from the start of randomization, with the primary event being death.

    Time frame: Death

    • Starting point: Randomization
    • Event: Death

Study contacts

Contact information is provided by the study sponsor or research team.

erlie jiang

CONTACT

[email protected]

15122538106

yigeng cao

CONTACT

[email protected]

18622477066

Sponsors and collaborators

Lead sponsor

Institute of Hematology & Blood Diseases Hospital, China

Other

Registry information

Official study title

Immediate Allogeneic Hematopoietic Stem Cell Transplantation Versus Re-treatment for Patients With High-Risk Acute Myeloid Leukemia: a Randomised, Open-label, Phase 2 Clinical Trial.

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Oct 16, 2024
Registry last updated
Dec 30, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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