Intermediate-dose HAD Regimen for CEBPA Double-mutated AML

NCT06529250 | Recruiting

• 1 other identifier: IIT2023005
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 1

Brief Summary

AML is highly heterogeneous in pathogenesis, and CEBPA double-mutated (CEBPAdm) AML is a common type of leukemia in China. Currently, no targeted therapies for CEBPAdm, and chemotherapy and transplantation are still the treatment options for CEBPA double-mutated AML. At present, the "3+7" treatment induction regimen of cytarabine combined with anthracyclines is still the first-line recommended regimen. In our retrospective study, the intermediate dose HAD regimen produced a 3-year RFS of 84.7% and a 3-year OS of 92.8% in CEBPAdm AML. Therefore, this project intends to confirm the efficacy of intermediate-dose HAD in the treatment of CEBPA double-mutated AML is superior to the conventional treatment regimen through the multi-center RCT study.

Conditions

AML

Keywords

AML; CEBPA double-mutated; treatment

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  The interval from randomization to assessment of response after the second course of chemotherapy treatment if patients failed to achieve CR after two courses of induction therapy, the date of relapse, or the date of death, whichever occurred first.

  up to 2 years after the date of the last enrolled participants

Secondary Outcomes (8)

• Complete response rate (CR)

  Six weeks after induction therapy

• 30-day mortality

  Within 30 days of randomization

• overall survival

  up to 2 years after the date of the last enrolled participants

• Event-free survival censored at hematopoietic stem cell transplantation

  up to 2 years after the date of the last enrolled participants

• Relapse free survival censored at hematopoietic stem cell transplantation

  up to 2 years after the date of the last enrolled participants

Study Arms (2)

intermediate-dose HAD regimen

EXPERIMENTAL

Patients received intermediate-dose HAD regimen. When patients reach complete remission (CR) after the induction therapy, 3 courses of the high-dose cytarabine regimen (3g/m2 q12h, 3 days) are used. Hematopoietic stem cell transplantation is recommended for patients with persistent MRD positive after treatment. When patients do not achieve CR after the induction therapy, reinduction therapy with IAC (IDA 10mg/m2 for 3 days, cytarabine 100mg/m2 for 7 days, cyclophosphamide 350mg/m2 d2, d5) regimen is used. Patients who still do not achieve CR after reinduction therapy will be removed from the group.

Drug: HAD

conventional treatment

ACTIVE COMPARATOR

Patients were treated with 3+7 induction regimen (IA or DA). When patients reach complete remission (CR) after the induction therapy, 3 courses of the high-dose cytarabine regimen (3g/m2 q12h, 3 days) are used. Hematopoietic stem cell transplantation is recommended for patients with persistent MRD positive after treatment. When patients do not achieve CR after the induction therapy, reinduction therapy with IAC (IDA 10mg/m2 for 3 days, cytarabine 100mg/m2 for 7 days, cyclophosphamide 350mg/ m2 d2, d5) regimen is used. Patients who still do not achieve CR after reinduction therapy will be removed from the group.

Drug: Daunorubicin+Cytarabine

Interventions

HAD DRUG

Induction therapy:Homoharringtonine: 2mg/㎡/d, days 1-7 Cytarabine: (Ara-c 100mg/㎡/d, day 1-4; 1g/㎡ /q12h, day 5-7), Daunorubicin: (DNR 40mg/㎡/d, day 1-3). Reinduction therapy: Idarubicin (IDA) 10mg/㎡ for d1-3 , Ara-c 100mg/㎡ d1-7 , Cyclophosphamide (CTX350mg/㎡ d2, d5) . Patients who did not achieve CR after reinduction therapy were removed from the group. After achieving CR, they received high-dose cytarabine (3g/m2 q12h, 3 days) regimen for consolidation for 3 courses. Hematopoietic stem cell transplantation is recommended for patients with persistent MRD positive after treatment.

Also known as: Homoharringtonine, Cytarabine, Daunorubicin

intermediate-dose HAD regimen

Daunorubicin+Cytarabine DRUG

Cytarabine: (Ara-c 100mg/㎡/d, day 1-7), Daunorubicin: (DNR 60mg/㎡/d, day 1-3) or idarubicin (IDA 12mg/㎡/d, day 1-3). Treatment did not achieve CR, and reinduction of IAC regimen was given. Reinduction therapy: Idarubicin (IDA) 10mg/㎡ ,d1-3, Ara-c 100mg/㎡ d1-7 , Cyclophosphamide (CTX350mg/㎡ d2, d5). Patients who did not achieve CR after reinduction therapy were removed from the group. After achieving CR, they received high-dose cytarabine (3g/m2 q12h, 3 days) regimen for consolidation for 3 courses. Hematopoietic stem cell transplantation is recommended for patients with persistent MRD positive after treatment.

Also known as: Cytarabine, Daunorubicin

conventional treatment

Eligibility Criteria

• Age: 14 Years - 54 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• AML diagnosed according to WHO-2022 classification with recurrent CEBPA mutations and containing mutation in the bZIP domain.
• Older than 14 years old and younger than 55 years old
• Male or female.
• The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of AML patients were 0-2 points.
• Meet the following laboratory tests (performed within 7 days prior to treatment) 1) Total bilirubin ≤ 1.5 times of the upper limit of normal value (same age); 2) AST and ALT≤ 2.5 times of the upper limit of normal value (same age); 3) Blood creatinine \< 2 times of the upper limit of normal value (same age); 4) Myocardial enzymes \< 2 times of the upper limit of normal value (same age); 5) Echocardiography (ECHO) was performed to determine the ejection fraction of the heart within the normal range.

You may not qualify if:

• Patients who have previously received induction chemotherapy, regardless of efficacy.
• Simultaneously suffering from malignant tumors of other organs and requiring treatment).
• Pregnant or lactating women. Male or female patients participating in the trial must take contraceptive measures during the trial treatment period.
• Active heart disease, defined as one or more of the following:1) Have a history of uncontrolled or symptomatic angina pectoris;2) Myocardial infarction less than 6 months prior to enrollment in the study;3) A history of arrhythmia requiring medication treatment or severe clinical symptoms;4) Uncontrolled or symptomatic congestive heart failure (\> NYHA grade 2);5) The ejection fraction is below the lower limit of the normal range.
• Serious infectious diseases (uncured tuberculosis, pulmonary aspergillosis).

Sponsors & Collaborators

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

Study Sites (1)

Blood Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

Related Publications (3)

• Wei H, Wang Y, Zhou C, Lin D, Liu B, Liu K, Qiu S, Gong B, Li Y, Zhang G, Wei S, Gong X, Liu Y, Zhao X, Gu R, Mi Y, Wang J. Distinct genetic alteration profiles of acute myeloid leukemia between Caucasian and Eastern Asian population. J Hematol Oncol. 2018 Feb 10;11(1):18. doi: 10.1186/s13045-018-0566-8.

  PMID: 29427994 RESULT

• Wei H, Zhou C, Liu B, Lin D, Li Y, Wei S, Gong B, Zhang G, Liu K, Gong X, Fang Q, Liu Y, Qiu S, Gu R, Song Z, Chen J, Yang M, Zhang J, Jin J, Wang Y, Mi Y, Wang J. The prognostic factors in acute myeloid leukaemia with double-mutated CCAAT/enhancer-binding protein alpha (CEBPAdm). Br J Haematol. 2022 May;197(4):442-451. doi: 10.1111/bjh.18113. Epub 2022 Mar 10.

  PMID: 35274287 RESULT

• Wei H, Wang Y, Gale RP, Lin D, Zhou C, Liu B, Qiu S, Gu R, Li Y, Zhao X, Wei S, Gong B, Liu K, Gong X, Liu Y, Zhang G, Song Z, Wang Y, Li W, Mi Y, Wang J. Randomized Trial of Intermediate-dose Cytarabine in Induction and Consolidation Therapy in Adults with Acute Myeloid Leukemia. Clin Cancer Res. 2020 Jul 1;26(13):3154-3161. doi: 10.1158/1078-0432.CCR-19-3433. Epub 2020 Feb 6.

  PMID: 32029439 RESULT

MeSH Terms

Interventions

Homoharringtonine; Cytarabine; Daunorubicin

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

Study Officials

• Hui Wei, MD

  Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hui Wei, MD

CONTACT

13132507161; weihui@ihcams.ac.cn

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: July 17, 2024
• First Posted: July 31, 2024
• Study Start: August 13, 2024
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): September 1, 2028
• Last Updated: January 16, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)