Clinical trial NCT06643195: 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.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: AML
Keywords: High-Risk Acute Myeloid Leukemia
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2024-10-16
Enrollment: 358
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

1. AML patients aged ≥ 18 years.
2. High-risk AML patients according to the 2022 ELN standards who received one cycle of induction therapy.
3. Requires allogeneic hematopoietic stem cell transplantation (including HLA-matched or mismatched allogeneic HSCT and unrelated donor transplant).
4. KPS score greater than 60.
5. 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:

1. Acute promyelocytic leukemia.
2. 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).
3. 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.

Primary outcomes:
measure: treatment success
timeFrame: day 56 after allogeneic HCT
Secondary outcomes:
measure: Cumulative Incidences of Allogeneic HSCT
timeFrame: HSCT rates at 4,8,16, and 24 weeks
measure: Incidence of Complete Remission from Randomisation
timeFrame: Date of first documented CR or CRi or CRchim Death before CR/CRi/CRchim not achieve a CR or CRi by six months
measure: Overall survival after HCT
timeFrame: Death
measure: Event-free survival after HCT
timeFrame: death before relapse, relapse (both, hematological or molecular), and failure to achieve a CR at final remission assessment
measure: Leukemia-free survival from day 56 after alloHCT for patients who met the primary endpoint
timeFrame: day 56
measure: Rate of MRD Negative from Day 56 after HSCT
timeFrame: day 56
measure: 7. Overall Survival from Randomization: Measured from the start of randomization, with the primary event being death.
timeFrame: Death
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: Hebei Medical University Second Hospital
state: Hebeisheng
city: Zhengzhou
country: China
facility: Zhengzhou University First Affiliated Hospital
state: Henan
city: Jinan
country: China
facility: The 960th Hospital of the Joint Service Support Force of the Chinese People's Liberation Army
state: Shandong
city: Chengdu
country: China
facility: People's Liberation Army The General Hospital of Western Theater Command
state: Sichuan
Study officials:
References: