Multicenter, Platform-type Clinical Study of Refractory/Recurrent Acute Myeloid Leukemia

August 5, 2026 updated by: Institute of Hematology & Blood Diseases Hospital, China
To study the optimal therapeutic strategies for salvage treatment of refractory/relapsed AML, and to clarify the effectiveness and safety of various salvage treatment options. A prospective, multicenter, platform-type study was conducted to explore the overall response rate, tolerability, and survival of patients with R/R AML with different treatment regimens.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

It is recommended to routinely screen for chromosomal karyotype, FLT3/ITD, FLT3/TKD and IDH1 mutations before enrollment.According to the patient's condition and physical condition, evaluate whether there is a suitable new drug clinical trial to enroll, if there is, enter the Arm 7 (new drug clinical trial); If not, enter other arm of the clinical study.According to the results of gene mutation, patients with target gene mutations should enter the corresponding study cohort (Arm1, Arm2), and select the regimen of specific targeted drug composition. For patients without a target mutation, patients eligible for intensive chemotherapy who had not received Venetoclax in the last 3 months were randomized to the Daunorubicin/idarbicin/mitoxantrone combination cytarabine + Venetoclax(DAV) (Arm3) and the Hyperhardinine combination cytarabine + Venetoclax cohort (HAV) (Arm4). Patients who were intolerant to intense chemotherapy were enrolled in the Venetoclax combined with Azacitidine cohort (Arm5). For patients who have failed treatment with Venetoclax within the last 3 months, the Venetoclax-based regimen is not recommended again and the physician is advised to conduct an exploratory trial (Arm6). After CR form induction therapy, allogeneic hematopoietic stem cell transplantation should be selected as far as possible according to the patient's wishes. For patients who are unable or unwilling to undergo allogeneic hematopoietic stem cell transplantation, physicians may choose post-remission consolidation therapy based on experience.

Study Type

Interventional

Enrollment (Estimated)

458

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Tianjin, China, 300020
        • Recruiting
        • Blood Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1. Patients with acute myeloid leukemia (except for acute promyelocytic leukemia) diagnosed by bone marrow cell morphology, immunology and genetics above are classified according to the French-British-American Collaboration diagnostic criteria (FAB criteria) and the World Health Organization diagnostic criteria (WHO2016 criteria).

    2. Meet criteria for refractory/recurrent AML (except APL). The recurrence was morphological recurrence, excluding molecular recurrence. Except for simple extramedullary leukemia.

    3. Age and gender are not limited. 4. Informed consent must be signed before the start of the study procedure, and the informed consent must be signed by the patient himself or his immediate family if he is 18 years old and above; For young patients under the age of 18, the legal guardian shall sign the informed consent. Considering the patient's condition, if the patient's signature is not conducive to the treatment of the condition, the informed consent shall be signed by the legal guardian or the patient's immediate family.

Exclusion Criteria:

  1. Concurrent malignant tumors of other organs (patients requiring treatment).
  2. Participants considered unsuitable for inclusion by the researchers.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 3
For R/R AML patients without IDH1 or FLT3 mutations who have not been exposed to Venecra in the last 3 months, the investigators will determine whether they are fit patients based on physical status and comorbidivities, and if they are, they can be randomly assigned to Arm3 or Arm4 DAV/IAV/MAV Cytarabine 100mg/m2/d, d1-5 Daunorubicin 60mg/m2/d, d1-2, or Idarubicin 12mg/m2/d, d1-2, or mitoxantrone 8mg/m2/d d1-2 Venetoclax 100mg d3, 200mg d4, 400mg d5-11;
Drug: Venetoclax
in arms 2-5
Drug: Cytarabine
in arms 3 and 7
Drug: Daunorubicin/ Idarubicin /Mitoxantrone
in arms 3 and 7
Experimental: Arm 6

Patients with R/R AML without IDH1 or FLT3 mutations who have been exposed to Vinecra within the last 3 months may be enrolled in the exploratory protocol group based on a comprehensive assessment of local drug availability and patient status:

Arm6:

The Investigator's choice (IC) option involves a range of drugs such as clatabine, PI3K inhibitors, histone deacetylase inhibitors, celinisol, and novel liposomes.
Drug: PI3K inhibitors, histone deacetylase inhibitors, selinexor, novel liposomal drugs, and others
in arm 6
Experimental: Arm 1

With IDH1 gene mutation(up to 2 cycles available):IVA :

Ivosidenib 500mg d1-28 Azacitidine 75mg/m2/d d1-7 Venetoclax100mg d1, 200mg d2, 400mg d3, 800mg d4-14, d14-28(If the proportion of bone marrow blasts on day 14 is greater than 5% )
Drug: Ivosidenib
in arm 1
Drug: Venetoclax
in arms 2-5
Drug: Azacitidine
in arms 1，2 , 5 and 8
Experimental: Arm 2

FLT3/ITD or FLT3/TKD gene mutation (up to 2 cycles available)

GVA:

Gilteritinib 80mg, d1-28 Azacitidine 75mg/m2/d d1-7 Venetoclax 100mg d1, 200mg d2, 400mg d3-14, 400mg d14-28 (if the proportion of bone marrow blasts on day 14 are greater than 5%)
Drug: Venetoclax
in arms 2-5
Drug: Azacitidine
in arms 1，2 , 5 and 8
Drug: Gilteritinib
in arm 2
Experimental: Arm 4

HAV :

Cytarabine 100mg/m2/d, d1-5; Homoharringtonine 2mg/m2 d1-5; Venetoclax 100mg d3, 200mg d4, 400mg d5-11
Drug: Venetoclax
in arms 2-5
Drug: Cytarabine
in arms 3 and 7
Drug: Homoharringtonine
in arms 4 and 7
Experimental: Arm 5

A patient with R/R AML without IDH1 or FLT3 mutation who has not been exposed to Venetoclax in the last 3 months but who is judged by the investigators to be unfit based on physical fitness and comorbidivities is unfit to enter Arm5.

Arm5: (up to 4 cycles available)

VA :

Azacytidine 75mg/m2/d d1-7; Venetoclax 100mg d1, 200mg d2, 400mg d3-21 400mg d22-28 (if the proportion of bone marrow blasts on day 21 are greater than 5%)
Drug: Venetoclax
in arms 2-5
Drug: Azacitidine
in arms 1，2 , 5 and 8
Experimental: Arm 7
DAV/IAV/MAV/HAV Regimen Cytarabine 100 mg/m²/day, days 1-5 Daunorubicin 60 mg/m²/day, days 1-2, or Idarubicin 12 mg/m²/day, days 1-2, or Mitoxantrone 8 mg/m²/day, days 1-2 / Homoharringtonine 2 mg/m²/day, days 1-5 Lisatoclax 200 mg on day 3, 400 mg on day 4, 600 mg on days 5-11
Drug: Cytarabine
in arms 3 and 7
Drug: Daunorubicin/ Idarubicin /Mitoxantrone
in arms 3 and 7
Drug: Homoharringtonine
in arms 4 and 7
Drug: Lisaftoclax
in arms 7 and 8
Experimental: Arm 8
Azacitidine 75 mg/m²/day, days 1-7 Lisatoclax 200 mg on day 1, 400 mg on day 2, 600 mg on days 3-21, and 600 mg on days 22-28 (if bone marrow blast percentage on day 21 is greater than 5%)
Drug: Azacitidine
in arms 1，2 , 5 and 8
Drug: Lisaftoclax
in arms 7 and 8

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complex response (CRc) rate (including CR and CRi)
Time Frame: up to 4 years
Proportion of patients with combined responses (complete and partial responses)
up to 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
mortality associated with salvage treatment (30 days, 60 days)
Time Frame: Treatment within 30 days and 60 days
Mortality of patients treated within 30 and 60 days
Treatment within 30 days and 60 days
MRD-negative complete response rate
Time Frame: the whole period of the trial, up to 730 days
Proportion of patients with complete response and MRD negative
the whole period of the trial, up to 730 days
Overall survival
Time Frame: the whole period of the trial, up to 730 days
Used to evaluate all patients entering clinical trials
the whole period of the trial, up to 730 days
Event-free survival
Time Frame: the whole period of the trial, up to 730 days
It is only used to evaluate patients who have achieved CR
the whole period of the trial, up to 730 days
Relapse-free survival
Time Frame: the whole period of the trial, up to 730 days.
It is only used to evaluate patients who have achieved CR
the whole period of the trial, up to 730 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 22, 2024

Primary Completion (Estimated)

January 30, 2028

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

January 17, 2024

First Submitted That Met QC Criteria

February 16, 2024

First Posted (Actual)

February 20, 2024

Study Record Updates

Last Update Posted (Actual)

August 7, 2026

Last Update Submitted That Met QC Criteria

August 5, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT2024001

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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