VHAG in Treating R/R T-ALL/LBL

Официальное название

Venetoclax Combined With HAG Regimen in Treating Adult Relapse/Refractory Acute T Cell Lymphoblastic Leukemia/Lymphoma: A Phase II, Single Arm and Multicenter Study

Обзор

Acute T cell lymphoblastic leukemia/lymphoma (T-ALL/LBL) is an aggressive type of leukemia that results from the malignant evolution of T-lineage progenitor cells at different differentiation stages. After induction chemotherapy and consolidation chemotherapy, there are still about 30% of patients who cannot achieve complete remission of clinical symptoms or negative MRD. This is also an important factor for the recurrence of ALL patients. In addition, most relapsed T-ALL/LBL patients relapse during first-line treatment. Once the disease relapses, it is difficult to cure for most young and adult patients, and the overall survival rate of patients is less than 10%.

Подробное описание

This is a prospective, single-arm, phase II and open-label study. A total of 50 R/R T-ALL/LBL participants will be enrolled. The primary endpoint is complete remission with or without peripheral blood cell recovery. The induction therapy is a combination of Venetoclax(Ven), Homoharringtonine(HHT) , Cytarabine and G-CSF. The purpose of this study is to explore efficacy of the VHAG in the treatment of R/R T-ALL/LBL patients.

Вмешательства

• Препарат Venetoclax
  BCL-2 inhibitor
• Препарат homoharringtonine
  alkaloid
• Препарат Cytarabine (Ara-C)
  Metabolic antagonist.
• Препарат G-CSF
  Granulocyte colony-stimulating factor

Первичные конечные точки

• Complete remission with or without incomplete PB cell recovery(CR/CRi) rate [Срок оценки: at the end of Cycle 1 and 2（each cycle is 28days）]

Вторичные конечные точки (4)

• Overall survival (OS) [Срок оценки: up to 5 years]
• Event free survival(EFS) [Срок оценки: up to 2 years]
• Minimal residual disease (MRD) [Срок оценки: At the end of Cycle 1 and 2（each cycle is 28 days）]
• Adverse event [Срок оценки: At the end of Cycle 1 and 2]

Критерии участия

Критерии включения

• 1\. Before enrollment, a diagnosis of newly diagnosed T-cell acute leukemia/lymphoma.The diagnostic criteria refer to the 2022 WHO classification; 2. Age ≥ 14 years,<75 years; 3. Clincally diagnosed as relapsed or refractory T-ALL/LBL; 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; 5. Expected survival time ≥ 2 months; 6. No organ dysfunction that would restrict the use of this protocol during the screening period; 7. Understand the study and sign the informed consent form.

Критерии исключения

• 1\. Patients with known central nervous system (CNS) involvement of T-ALL/LBL; 2. Diseases with abnormal heart, lung, liver, kidney, or other organ functions that may limit the patient's participation in this trial (including but not limited to severe infections, uncontrolled diabetes, severe heart failure or angina, active pulmonary tuberculosis, asthma, COPD, bronchiectasis, etc.) 3. Cardiac ultrasound LVEF < 45%; 4. History of other malignancies within the past 5 years, excluding localized thyroid cancer and in situ skin cancer; 5. Serum total bilirubin > 1.5 ULN (upper limit of normal); ALT or AST > 2.5 ULN; serum creatinine > 1.5 ULN; 6. Known HIV infection; 7. Conditions affecting the use of the study drug as assessed by the investigator; 8. Inability to understand or comply with the study protocol.

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

• The First Affiliated Hospital, Zhejiang University School of Medicine — Ханчжоу

Публикации

• Peirs S, Matthijssens F, Goossens S, Van de Walle I, Ruggero K, de Bock CE, Degryse S, Cante-Barrett K, Briot D, Clappier E, Lammens T, De Moerloose B, Benoit Y, Poppe B, Meijerink JP, Cools J, Soulier J, Rabbitts TH, Taghon T, Speleman F, Van Vlierberghe P. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood. 2014 Dec 11;124(25):3738- PMID 25301704
• Stock W, Luger SM, Advani AS, Yin J, Harvey RC, Mullighan CG, Willman CL, Fulton N, Laumann KM, Malnassy G, Paietta E, Parker E, Geyer S, Mrozek K, Bloomfield CD, Sanford B, Marcucci G, Liedtke M, Claxton DF, Foster MC, Bogart JA, Grecula JC, Appelbaum FR, Erba H, Litzow MR, Tallman MS, Stone RM, Larson RA. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemi PMID 30658992
• Dunsmore KP, Winter SS, Devidas M, Wood BL, Esiashvili N, Chen Z, Eisenberg N, Briegel N, Hayashi RJ, Gastier-Foster JM, Carroll AJ, Heerema NA, Asselin BL, Rabin KR, Zweidler-Mckay PA, Raetz EA, Loh ML, Schultz KR, Winick NJ, Carroll WL, Hunger SP. Children's Oncology Group AALL0434: A Phase III Randomized Clinical Trial Testing Nelarabine in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia. J PMID 32813610
• Quist-Paulsen P, Toft N, Heyman M, Abrahamsson J, Griskevicius L, Hallbook H, Jonsson OG, Palk K, Vaitkeviciene G, Vettenranta K, Asberg A, Frandsen TL, Opdahl S, Marquart HV, Siitonen S, Osnes LT, Hultdin M, Overgaard UM, Wartiovaara-Kautto U, Schmiegelow K. T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol. Leukemia. 2020 Feb;34(2):347-3 PMID 31611626
• Chiaretti S, Vitale A, Cazzaniga G, Orlando SM, Silvestri D, Fazi P, Valsecchi MG, Elia L, Testi AM, Mancini F, Conter V, te Kronnie G, Ferrara F, Di Raimondo F, Tedeschi A, Fioritoni G, Fabbiano F, Meloni G, Specchia G, Pizzolo G, Mandelli F, Guarini A, Basso G, Biondi A, Foa R. Clinico-biological features of 5202 patients with acute lymphoblastic leukemia enrolled in the Italian AIEOP and GIMEMA PMID 23716539

Идентификаторы

NCT: NCT06742463 · IIT20240113C

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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