Bortezomib Combined With DAG Regimen in the Treatment of Refractory/Relapsed AML

NCT05982756 | Unknown Phase 1 DMC

• 1 other identifier: 04
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

In recent years, the efficacy of AML has been greatly improved, which is mainly due to the following aspects: the development of individualized treatment strategies based on genetic prognosis stratification, the application of high-dose cytarabine-containing induction and consolidation regimens , the choice of allogeneic or autologous hematopoietic stem cell transplantation, etc. However, 20%-30% of young patients and 40%-50% of elderly patients will relapse again, and 20%-40% of patients cannot be relieved after standard induction regimens, that is, relapsed and refractory AML. The re-induction remission rate is low, the survival period is short, and the prognosis is extremely poor. There is still a lack of standard treatment options. Although a small number of patients can benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT), most patients lack suitable donors. The choice of high-dose chemotherapy is a salvage treatment option, but treatment-related hematological or non-hematological toxicities and high lethality make the option controversial, especially for the elderly. The development of new low-toxic targeted drugs is a future trend, and the design of new efficient and safe chemotherapy regimens is also a way of thinking. This study designed a prospective single-center clinical randomized controlled study plan, that is, the use of bortezomib (1.3mg/m2, d1, 4, 8, 11) combined with DAG regimen in the treatment of refractory/relapsed AML, to evaluate the clinical efficacy (complete remission rate , total effective rate, 2-year progression-free survival rate and 2-year overall survival rate), and observe how safe the new program is. The results of the research will make it possible to design a high-efficiency, low-toxicity and high-feasibility chemotherapy regimen for refractory/relapsed patients, and guide the clinical treatment of relapsed/refractory acute leukemia.

Conditions

Bortezomib; Acute Myeloid Leukemia

Keywords

pre-excitation regimen; acute myeloid leukemi; Bortezomib

Outcome Measures

Primary Outcomes (1)

• Rate Rate of bone marrow blasts

  Bone marrow blasts \<20%

  Evaluation at the 4th weekend after the end of all chemotherapy cycles

Secondary Outcomes (5)

• blood routine

  Evaluation at the 4th weekend after the end of all chemotherapy cycles

• liver function

  Evaluation at the 4th weekend after the end of all chemotherapy cycles

• Recovery time

  Evaluation at the 4th weekend after the end of all chemotherapy cycles

• The incidence of complications in patients

  Evaluation at the 4th weekend after the end of all chemotherapy cycles

• kidney function

  Evaluation at the 4th weekend after the end of all chemotherapy cycles

Study Arms (2)

Test group: Induction treatment plan A

EXPERIMENTAL

Bortezomib+DAG pre-excitation regimen

Drug: DAG pre-excitation regimen with Bortezomib

Control group: induction regimen B

ACTIVE COMPARATOR

DAG pre-excitation plan alone

Drug: DAG pre-excitation regimen with Bortezomib

Interventions

DAG pre-excitation regimen with Bortezomib DRUG

Bortezomib+DAG pre-excitation regimen: Bortezomib (specification 3.5mg, intravenous injection, 4 times a course of treatment, 1.3mg/m2, d1, 4, 8, 11; doxorubicin liposome injection 5 mg/ m2, intravenous infusion, once every other day, 5 times in total; cytarabine 10 mg/m2 every 12 hours, subcutaneous injection, d1-14; G-CSF 200 μg/m2 daily, subcutaneous injection, d1-14 Days, WBC \>10×109/L during chemotherapy, postpone the use until it falls below this value;

Also known as: Bortezomib group

Control group: induction regimen B; Test group: Induction treatment plan A

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with AML confirmed by bone marrow morphology and immunology
• Patients who do not respond or relapse after conventional treatment
• Age 18-75
• Liver and kidney function: blood bilirubin ≤ 35 μmol/L, AST/ALT below 2 times the upper limit of normal value, 451 μmol/L ≥ serum creatinine ≥ 133 μmol/L, 80 ml/min ≥ creatinine clearance ≥ 20ml/min
• Cardiac function index EF value ≥ 50%
• Physical condition score 0-2 (ECOG score)
• Obtain signed informed consent from patients or family members

You may not qualify if:

• Allergies or obvious contraindications to any of the drugs involved in the program
• Severe heart disease, including myocardial infarction and cardiac insufficiency.
• Suffering from other organ malignancies at the same time
• Active tuberculosis patients and HIV positive patients
• Suffering from other blood system diseases at the same time
• Pregnant or lactating women
• Inability to understand or follow the research protocol
• \. Past history of intolerance or allergy to similar drugs 2. Patients under 18 years old or over 75 years old 3. Simultaneously participate in other clinical investigators 4. Any other circumstances that prevent the conduct of the study

Sponsors & Collaborators

• Zhongnan Hospital: lead

Study Sites (1)

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430071, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Fuling Zhou, phD

  Wuhan University

  STUDY DIRECTOR

• TIANZHI WU, phD

  Wuhan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fuling Zhou, phD

CONTACT

+86-27-67811840; zhoufuling@whu.edu.cn

Tianzhi Wu, phD

CONTACT

+86-27-67811840; wutianzhi@whu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Remove masking if necessary
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2023
• First Posted: August 9, 2023
• Study Start: January 1, 2020
• Primary Completion: September 1, 2023
• Study Completion: December 1, 2023
• Last Updated: August 9, 2023

Record last verified: 2023-03

Locations

CN (1)