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

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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: AML
• Intervention / Treatment: Other: ImmediateAllogeneic Hematopoietic Stem Cell Transplantation; Other: Retreatment

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.

• Study Type: Interventional
• Enrollment (Estimated): 358
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: yigeng cao; Phone Number: 18622477066; Email: caoyigeng@ams.ac.cn
• Study Contact Backup: Name: erlie jiang; Phone Number: 15122538106; Email: jiangerlie@ihcams.ac.cn

Study Locations

• China
  • Hebeisheng
    • Shijiazhuang, Hebeisheng, China, 050000
      • Hebei Medical University Second Hospital
      • Contact: xuejun zhang; Phone Number: +86-13722781112
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Zhengzhou university first affiliated hospital
      • Contact: weijie cao; Phone Number: +86-15093360671; Email: 945509679@qq.com
  • Shandong
    • Jinan, Shandong, China
      • The 960th Hospital of the Joint Service Support Force of the Chinese People's Liberation Army
      • Contact: FANG ZHOU; Phone Number: +86-13969179221
  • Sichuan
    • Chengdu, Sichuan, China, 610083
      • People's Liberation Army The General Hospital of Western Theater Command

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.
Active Comparator: 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).	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).

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Incidences of Allogeneic HSCT	Starting point: Randomization; Event: allogeneic HCT; Competing events: death, withdrawal	HSCT rates at 4,8,16, and 24 weeks
Incidence of Complete Remission from Randomisation	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	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	Starting point: HCT; Event: Death	Death
Event-free survival after HCT	Starting point: HCT; Events: death before relapse, relapse (both, hematological or molecular), and failure to achieve a CR at final remission assessment	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	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	day 56
Rate of MRD Negative from Day 56 after HSCT	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	day 56
7. Overall Survival from Randomization: Measured from the start of randomization, with the primary event being death.	Starting point: Randomization; Event: Death	Death

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: September 22, 2024
• First Submitted That Met QC Criteria: October 14, 2024
• First Posted (Actual): October 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 27, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: High-Risk Acute Myeloid Leukemia
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: IIT2024063

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No