Molecular Subtype Combined with Early Minimal Residual Disease to Optimize the Treatment of Newly Diagnosed Acute Myeloid Leukemia

NCT06652685 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: IA+X 2024
• Study Type: interventional
• Target: 218
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the safety and efficacy of drug "X" in combination with intensive chemotherapy in subjects with newly diagnosed AML (excluding APL and CBF-AML). "X" drugs included BCL-2 inhibitor venetoclax and FLT3 inhibitor Gilteritinib. Subjects will receive standard intensive chemotherapy during induction and consolidation. Early induction response will be evaluated according to the results of peripheral blood blast clearance rate on the fifth day after induction therapy (D5-PBCR). Venetoclax will be added in D5-PBCR positive subjects. For subjects with FLT3 mutations, Gilteritinib will be combined. Subjects will be stratified based on the genetic risk classification of 2022 European LeukemiaNet recommendations (ELN risk) and MRD status to receive specific consolidation therapy after the induction therapy.

Conditions

Acute Myeloid Leukemia (AML)

Keywords

Acute myeloid leukemia; venetoclax; gilteritinib; D5-PBCR; Risk-stratified

Outcome Measures

Primary Outcomes (1)

• Composite complete remission rate

  Complete remission/complete remission with partial hematological recovery/complete remission with incomplete hematological recovery

  At the end of cycle one (up to 42 days from the start of cycle 1）

Secondary Outcomes (5)

• Total composite complete remission rate

  At the end of induction cycle 2 (up to 42 days from the start of cycle 2)

• OS

  2-year

• EFS

  2-year

• AE

  Throughout the entire study period, an average of 1 year

• Recovery time for neutrophils and platelets

  During induction cycle one (up to 42 days from the start of cycle 1)

Other Outcomes (2)

• The complete remission rate of MRD negative

  at the end of induction (up to 42 days from the start of induction cycle 2) and consolidation stage (after two cycles of consolidation, up to 42 days from the start of consolidation cycle 2)

• biomarkers of apoptosis

  Throughout the entire study period, an average of 1 year

Study Arms (2)

D5-PBCR(-)

EXPERIMENTAL

On day five of IA induction, D5-PBCR will be tested according to protocol. For D5-PBCR (-) patients, no additional of venetoclax is needed.

Drug: D5-PBCR(-) IA arm

D5-PBCR(+)

EXPERIMENTAL

On day five of induction, D5-PBCR will be tested according to protocol. D5-PBCR (+) patients, will receive induction therapy consisting of venentoclax combined with IA regimen.

Drug: D5-PBCR(+) IA+Venetoclax arm

Interventions

D5-PBCR(-) IA arm DRUG

Induction: IA Drug: idarubicin, intravenously, 10 mg/m\^2 on D1-3 Drug: cytarabine, intravenously, 100 mg/m\^2 on D1-7 Consolidation: Subjects who achieve composite complete remission (CRc) proceed with consolidation therapy. In consolidation therapy phase, subjects in the group with favorable/intermediate risk and MRD negetive, will receive cytarabine intravenously at 2g/m\^2/q12h\*6 doses. Subjects in the group with adverse risk or MRD positive will receive cytarabine intravenously at 2g/m\^2/q12h\*6 doses together with venetoclax 400mg on D4-10. Dose ramp-up of venetoclax is not required. After two cycles of consolidation, a multi-disciplinary team will discuss whether the patient need allogeneic hematopoietic stem-cell transplant (allo-HSCT) according to ELN risk stratification and MRD status.

D5-PBCR(-)

D5-PBCR(+) IA+Venetoclax arm DRUG

Induction: IA+Ven Drug: idarubicin, intravenously, 10 mg/m\^2, on D1-3, Drug: cytarabine, intravenously, 100 mg/m\^2 on D1-7 For D5-PBCR (+) patients, Venetoclax will be combined. Drug: Venetoclax. Orally once daily, on D6-14. A 3-day dose ramp-up is required for the first induction (100mg D6, 200mg D7, 400mg D8-14) If a second induction is needed, the dose of IA is the same as the first cycle, and dose ramp-up of venetoclax is not required. Consolidation: Subjects who achieve composite complete remission (CRc) proceed with consolidation therapy. In consolidation therapy phase, subjects in the group will receive cytarabine intravenously at 2g/m\^2/q12h\*6 doses together with venetoclax 400mg on D4-10. Dose ramp-up of venetoclax is not required. After two cycles of consolidation, a multi-disciplinary team will discuss whether the patient need allogeneic hematopoietic stem-cell transplant (allo-HSCT) according to ELN risk stratification and MRD status.

D5-PBCR(+)

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Bone marrow morphology and immunology confirmed newly diagnosed AML patients (according to 2022 ICC criteria)
• Exclude patients with APL and CBF-AML (according to fusion genes and chromosomes)
• Performance status score 0-2 (ECOG score)
• Age 18\~59 years old
• Liver and kidney function: blood bilirubin ≤ 35 μmol/L, AST/ALT below 2 times the upper limit of normal, creatinine ≤ 150 μmol/L
• Normal cardiac function (EF ≥50%)
• Obtained informed consent signed by the patient or family member

You may not qualify if:

• FAB classification is M3, or confirmed APL at the molecular level
• CBF-AML
• Patients who have already been treated
• Comfirmed central nervous system leukemia
• Allergy to any of the drugs involved in the protocol
• Medical condition or organ system dysfunction that precludes the inability to swallow capsules or tablets, or has a disease that significantly affects gastrointestinal function and/or inhibits small bowel absorption (including malabsorption syndrome, small bowel resection, or poorly controlled inflammatory bowel disease)
• Cardiac function and disease consistent with one of the following: a) long QTc syndrome or QTc interval \>480 ms; b) second- or third-degree atrioventricular block; Severe, uncontrolled cardiac arrhythmias requiring medication; c) United States New York College of Cardiology Grade ≥ III; d) Ventricular ejection fraction (LVEF) less than 50%; e) History of myocardial infarction, unstable angina, severe unstable ventricular arrhythmia or any other arrhythmia requiring treatment, history of clinically severe pericardial disease, or ECG evidence of acute ischemic or active conduction abnormalities within 6 months prior to recruitment
• Previous or present concomitant malignancies (except for basal cell carcinoma of the skin that have been effectively controlled as non-melanoma, carcinoma in situ of the breast/cervix, and other malignancies that have not been effectively controlled for more than 6 months, and patients who have been receiving long-term non-chemotherapy treatments such as hormonal therapy)
• Significant abnormalities in liver and kidney function (serum bilirubin, aspartate aminotransferase, alanine aminotransferase or serum creatinine more than 2 times the upper limit of normal reference values; Excluded from AML-related as judged by the investigator)
• Patients who have previously used other drugs for the treatment of AML (except hydroxyurea and cytarabine for cell count control), including but not limited to BCL2, FLT3, IDH1, IDH2 inhibitors, or other drugs in clinical trials
• Coagulopathy not associated with AML
• HIV infection, syphilis infection, HCV infection, active HBV infection (HBsAg positive, or HBsAg negative but HBcAb positive with HBV DNA \> 1.0 ×ULN)
• Other uncontrolled active infection (as judged by the investigator)
• Pregnant or lactating women
• Inability to understand or follow the study protocol

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, China

Location

Related Publications (2)

• Zhang Y, Li X, Weng X, Shen Y, Chen Y, Zheng Y, Zhao H, You J, Mao Y, Wang L, Wu M, Sheng Y, Wu J, Hu J, Chen Q, Li J. Optimization of idarubicin and cytarabine induction regimen with homoharringtonine for newly diagnosed acute myeloid leukemia patients based on the peripheral blast clearance rate: A single-arm, phase 2 trial (RJ-AML 2014). Am J Hematol. 2022 Jan 1;97(1):43-51. doi: 10.1002/ajh.26386. Epub 2021 Nov 1.

  PMID: 34687467 BACKGROUND

• Yu C, Kong QL, Zhang YX, Weng XQ, Wu J, Sheng Y, Jiang CL, Zhu YM, Cao Q, Xiong SM, Li JM, Xi XD, Chen SJ, Chen B. Clinical significance of day 5 peripheral blast clearance rate in the evaluation of early treatment response and prognosis of patients with acute myeloid leukemia. J Hematol Oncol. 2015 May 10;8:48. doi: 10.1186/s13045-015-0145-1.

  PMID: 25957890 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Yang Shen

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yunxiang Zhang

CONTACT

+86-13564516001; zyx12103@rjh.com.cn

Hongming Zhu

CONTACT

+86-15921512422; zhm11931@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Director of Hematology Division

Model Details: Subjects receive IA regimen as the initial induction. On day five of induction, D5-PBCR will be tested according to protocol. Patients will be assigned to different arms according to the result of D5-PBCR. For FLT3 mutate patients, a combination of gilteritinib will be recommended in this study. Induction and consolidation phase: gilteritinib 80mg on D8-14.

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 22, 2024
• Study Start: October 30, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: October 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)