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

NCT06265545 | Recruiting

• 1 other identifier: IIT2024001
• Study Type: interventional
• Target: 458
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

AML; Refractory; Relapsed

Keywords

AML; Refractory; Relapsed

Outcome Measures

Primary Outcomes (1)

• Complex response (CRc) rate (including CR and CRi)

  Proportion of patients with combined responses (complete and partial responses)

  up to 4 years

Secondary Outcomes (5)

• mortality associated with salvage treatment (30 days, 60 days)

  Treatment within 30 days and 60 days

• MRD-negative complete response rate

  the whole period of the trial, up to 730 days

• Overall survival

  the whole period of the trial, up to 730 days

• Event-free survival

  the whole period of the trial, up to 730 days

• Relapse-free survival

  the whole period of the trial, up to 730 days.

Study Arms (8)

Arm 1

EXPERIMENTAL

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; Drug: Venetoclax; Drug: Azacitidine

Arm 2

EXPERIMENTAL

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; Drug: Gilteritinib; Drug: Azacitidine

Arm 3

EXPERIMENTAL

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; Drug: Cytarabine; Drug: Daunorubicin/ Idarubicin /Mitoxantrone

Arm 4

EXPERIMENTAL

HAV : Cytarabine 100mg/m2/d, d1-5; Homoharringtonine 2mg/m2 d1-5; Venetoclax 100mg d3, 200mg d4, 400mg d5-11

Drug: Venetoclax; Drug: Homoharringtonine; Drug: Cytarabine

Arm 5

EXPERIMENTAL

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; Drug: Azacitidine

Arm 6

EXPERIMENTAL

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

Arm 7

EXPERIMENTAL

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: Homoharringtonine; Drug: Cytarabine; Drug: Daunorubicin/ Idarubicin /Mitoxantrone; Drug: Lisaftoclax

Arm 8

EXPERIMENTAL

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; Drug: Lisaftoclax

Interventions

Ivosidenib DRUG

in arm 1

Arm 1

Venetoclax DRUG

in arms 2-5

Arm 1; Arm 2; Arm 3; Arm 4; Arm 5

Gilteritinib DRUG

in arm 2

Arm 2

Homoharringtonine DRUG

in arms 4 and 7

Arm 4; Arm 7

Cytarabine DRUG

in arms 3 and 7

Arm 3; Arm 4; Arm 7

Daunorubicin/ Idarubicin /Mitoxantrone DRUG

in arms 3 and 7

Arm 3; Arm 7

Azacitidine DRUG

in arms 1，2 , 5 and 8

Arm 1; Arm 2; Arm 5; Arm 8

Lisaftoclax DRUG

in arms 7 and 8

Arm 7; Arm 8

PI3K inhibitors, histone deacetylase inhibitors, selinexor, novel liposomal drugs, and others DRUG

in arm 6

Arm 6

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Concurrent malignant tumors of other organs (patients requiring treatment).

Sponsors & Collaborators

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

Study Sites (1)

Blood Hospital

Tianjin, 300020, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

ivosidenib; venetoclax; gilteritinib; Homoharringtonine; Cytarabine; Daunorubicin; Idarubicin; Mitoxantrone; Azacitidine; Lisaftoclax; Histone Deacetylase Inhibitors; selinexor

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Harringtonines; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Anthraquinones; Anthrones; Anthracenes; Quinones; Aza Compounds; Ribonucleosides; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2024
• First Posted: February 20, 2024
• Study Start: February 22, 2024
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: August 7, 2026

Record last verified: 2026-08

Locations

CN (1)