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

Official 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.

Overview

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.

Detailed description

1. 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. 2. 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.

Interventions

• Other ImmediateAllogeneic Hematopoietic Stem Cell Transplantation
  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.
• Other Retreatment
  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 outcome measures

• treatment success [Time frame: day 56 after allogeneic HCT]

Secondary outcome measures (7)

• Cumulative Incidences of Allogeneic HSCT [Time frame: HSCT rates at 4,8,16, and 24 weeks]
• 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]
• Overall survival after HCT [Time frame: Death]
• 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]
• Leukemia-free survival from day 56 after alloHCT for patients who met the primary endpoint [Time frame: day 56]
• Rate of MRD Negative from Day 56 after HSCT [Time frame: day 56]
• 7. Overall Survival from Randomization: Measured from the start of randomization, with the primary event being death. [Time frame: Death]

Eligibility criteria

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:

1\) 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.

4\) 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 4 centers

• Hebei Medical University Second Hospital — Shijiazhuang
• Zhengzhou University First Affiliated Hospital — Zhengzhou
• The 960th Hospital of the Joint Service Support Force of the Chinese People's Liberation A — Jinan
• People's Liberation Army The General Hospital of Western Theater Command — Chengdu

Identifiers

NCT: NCT06643195 · IIT2024063

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗