Venetoclax-containing Therapy Combined With Microtransplant for Intermediate-risk and Higher MDS

Официальное название

Phase 2 Study of Venetoclax-containing Therapy in Combination With HLA-mismatched Mobilized Peripheral Blood Mononuclear Cell Infusion for Intermediate-risk and Higher Myelodysplastic Syndromes

Обзор

This study aims to evaluate the safety and efficacy of a Venetoclax and hypomethylating agent-based regimen combined with infusion of HLA-mismatched donor G-CSF mobilized peripheral blood mononuclear cells (GPBMC) in patients with intermediate-risk and higher myelodysplastic syndromes who are ineligible for allogeneic hematopoietic stem cell transplantation.

Вмешательства

• Препарат Venetoclax
  Given PO. For the first cycle, dose of 100 mg on Day 1, 200 mg on Day 2, and 400 mg on Days 3-14. For other cycles, dose of 400 mg on Days 1-14. Note: The dose should be reduced to 100-200 mg daily if concomitant azole antifungals are required.
• Препарат Azacitidine (AZA) or Decitabine (DAC)
  AZA: Given SC. Dose of 75 mg/m² on Days 1-7 of each cycle. DAC: Given IV. Dose of 20 mg/m² on Days 1-5 of each cycle.
• Биопрепарат GPBMC infusion
  HLA-mismatched donor GPBMCs are infused on Day 15.

Первичные конечные точки

• Overall survival (OS) [Срок оценки: Measured up to 4 years after the last participant is enrolled]
• Overall response rate (ORR) [Срок оценки: Measured up to 2 years after the last participant is enrolled]

Вторичные конечные точки (7)

• Modified overall response (mOR) [Срок оценки: Measured up to 2 years after the last participant is enrolled]
• Complete remission (CR) [Срок оценки: Measured up to 2 years after the last participant is enrolled]
• Partial remission (PR) [Срок оценки: Measured up to 2 years after the last participant is enrolled]
• CR with limited count recovery (CRL) [Срок оценки: Measured up to 2 years after the last participant is enrolled]
• CR with partial hematologic recovery (CRh) [Срок оценки: Measured up to 2 years after the last participant is enrolled]
• Progression-free survival (PFS) [Срок оценки: Measured up to 4 years after the last participant is enrolled]
• Treatment-related mortality (TRM) [Срок оценки: Measured up to 2 years after the last participant is enrolled]

Критерии участия

Критерии включения

• Age >=18 years, male or female, non-limited by race or ethnicity.
• Confirmed diagnosis of MDS according to the World Health Organization (WHO) 5th edition classification, based on histopathology and cytogenetics.
• Risk stratification according to the Revised International Prognostic Scoring System (IPSS-R) must place the patient in the intermediate-, high-, or very high-risk category.
• Not candidates for or refuse allogeneic hematopoietic stem cell transplantation.
• Adequate hepatic function including alanine transaminase (ALT) and aspartate aminotransferase (AST )<= 3 × upper limit of normal(ULN), and total bilirubin <= 1.5 × ULN.
• Adequate renal function including serum creatinine <= 2 × ULN or CrCl>= 40mL/min.
• LVEF measured by echocardiogram is within the normal range (LVEF > 50%).
• The subject must have one donor who is >= 18 years old and HLA matched at 0-7/10 loci (i.e., at least 3 HLA loci must be mismatched). In addition, the donor voluntarily donates hematopoietic stem cells and signs the consent form.
• Each subject (or his/her legal representatives) must sign the Informed Consent Form (ICF), indicating that he/she understands the purpose and procedures of research, and is willing to participate in research.
• Donor inclusion criteria: The donor meets the institution's criteria for related peripheral blood hematopoietic stem cell donors. The donor must be able to tolerate the cell separation and collection process, and sign the Informed Consent Form.

Критерии исключения

• Uncontrolled infection or hemorrhage.
• Cardiovascular disease with clinical significance, such as uncontrolled or highly symptomatic cardiac arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior to screening, or New York Heart Association (NYHA) function class 3 (moderate) or class 4 (severe) heart disease.
• Uncontrolled autoimmune disease or requiring immunosuppression treatment.
• History of severe blood infusion reaction.
• Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception.
• Psychiatric disorder or cognitive impairment that in the researcher's judgment would make the subject not likely to adhere to the protocol requirements.
• Major surgery within 4 weeks prior to enrollment.
• Life-threatening illness other than MDS or uncontrolled intercurrent illness.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital — Пекин

Идентификаторы

NCT: NCT07238686 · VEN-MST for MDS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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