A Study to Investigate LP-118, Ponatinib, Vincristine and Dexamethasone in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LBL)

Официальное название

A Phase I/II Study to Investigate the Combination of LP-118, Ponatinib, Vincristine and Dexamethasone in Relapsed/Refractory T-ALL/LBL

Обзор

The purpose of this study is to learn more about LP-118 (an experimental drug) and its side effects and decide on acceptable doses. The purpose of this study is to determine if LP-118 can be given safely with another medicine called ponatinib, that is FDA-approved for the treatment of acute lymphoblastic leukemia.

Подробное описание

The purpose of this study is to learn more about LP-118 (an experimental drug) and its side effects and decide on acceptable doses. The purpose of this study is to determine if LP-118 can be given safely with another medicine called ponatinib, that is FDA-approved for the treatment of acute lymphoblastic leukemia.

This study will investigate the combination of LP-118 and ponatinib at different dose levels to find the best doses that can be safely given to patients. This means that enrolled subjects will receive progressive increasing or decreasing doses of these drugs until the maximally tolerated dose is determined. All participants will also receive a standard of care chemotherapy combination consisting of the FDA approved drugs vincristine, dexamethasone and intrathecal (injection into the spinal canal, also called "spinal tap") methotrexate. This combination is standard of care for relapsed T-ALL/LBL.

Вмешательства

• Препарат LP-118
  LP-118 is an experimental anti-cancer drug that is currently being studied in clinical trials for multiple types of hematological cancers and solid tumors.
• Препарат Ponatinib
  Ponatinib is used to treat certain types of chronic myeloid leukemia (CML; a type of cancer of the white blood cells).
• Препарат Vincristine
  Vincristine is a chemotherapy medication used to treat various types of cancer, including leukemia, lymphoma, neuroblastoma, and Wilms tumor. Vincristine belongs to the category of vinca alkaloids, a class of drugs that function by impeding the proper division of cancer cells.
• Препарат Dexamethasone
  Dexamethasone is used to treat cancer, to decrease inflammation and sometimes used before and after chemotherapy to prevent or treat nausea and/or vomiting. It is given in the vein (IV) or orally (by mouth)
• Препарат Methotrexate
  Methotrexate is a drug used to treat cancer of the blood, bone, lung, breast, head, and neck. It can also treat rheumatoid arthritis and psoriasis.

Первичные конечные точки

• Recommended Phase II Dose To demonstrate safety and to identify the recommended phase II dose for combination of LP-118, ponatinib, vincristine and dexamethasone [Срок оценки: 36 weeks]

Вторичные конечные точки (6)

• Complete Clinical Remission at Days 28 and 56 [Срок оценки: 36 weeks]
• Complete clinical remission with incomplete count recovery (CRi) at Days 28 and 56 [Срок оценки: 36 weeks]
• Complete Clinical Remission (CR) with Measurable Residual Disease (MRD) [Срок оценки: 36 weeks]
• Complete clinical remission with incomplete count recovery (CRi) with Measurable Residual Disease (MRD) [Срок оценки: 36 weeks]
• Overall Survival [Срок оценки: 36 weeks]
• Progression-Free Survival [Срок оценки: 36 weeks]

Критерии участия

Критерии включения

• Relapsed or refractory patients with T-lineage acute lymphoblastic leukemia or T-lymphoblastic lymphoma
• 18 years old or older
• Bone marrow or peripheral blood involvement with ≥5% lymphoblasts or measurable residual disease with >10-4 level detected by multiparameter flow cytometry or next-generation sequencing (NGS)-based measurable residual disease (ClonoSEQ, Adaptive Technologies). Patients with isolated extramedullary disease that is measurable by computed tomography (CT) scan are also eligible.
• Eastern Cooperative Oncology Group performance status 0-2.
• Adequate organ function as defined by all of the following:

• Creatinine clearance ≥50 mL/min, determined by the Cockroft-Gault formula, or measured by a 24-hour urine collection.
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN) and bilirubin ≤1.5 x ULN (unless considered due to Gilbert's syndrome or of non-hepatic origin i.e,, leukemic involvement). For patients with Gilbert's syndrome, bilirubin ≤1.5 x of their baseline bilirubin level will be required.
• Participants must be at least 2 weeks from major surgery or radiation therapy. A wash-out period of 4 half-lives is required for patients who participated in other investigational trials. These patients must have recovered from clinically significant toxicities related to these prior treatments.
• Participants must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
• Females of childbearing potential will use effective contraception during protocol treatment and for at least 8 months after the last dose. Males with female partners of reproductive potential will use effective contraception during protocol treatment and for at least 5 months after the last dose. A patient is of childbearing potential if, in the opinion of the treating investigator, he/she is biologically capable of having children and is sexually active. Female patients who are not of childbearing potential (ie, meet at least one of the following criteria):

a. Have undergone hysterectomy or bilateral oophorectomy; or have medically confirmed ovarian failure; or are medically confirmed to be post-menopausal (cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause).

• Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Критерии исключения

• Active central nervous system (CNS) leukemia
• Active or chronic hepatitis B or C infection as evidenced by hepatitis B surface antigen and anti-hepatitis C antibody positivity, respectively, or known seropositivity for human immunodeficiency virus (HIV). Patients with HIV but an undetectable viral load are eligible for enrollment.
• Major surgery within <2 weeks before randomization.
• Unstable or severe uncontrolled medical condition (eg, unstable cardiac function or unstable pulmonary condition.
• Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer that has been definitely treated with radiation or surgery. Patients with previous malignancies are eligible provided that they have been disease free for ≥2 years or are not currently requiring treatment.
• Uncontrolled cardiac disease.
• Pregnant females; breastfeeding females; males with female partners of reproductive potential and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for a minimum of 5 months after the last dose of investigational product if male and 8 months after the last dose of investigational product if female.
• Participation in other investigational studies during active treatment phase.
• Other severe acute, chronic medical, psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the treating physician, would make the patient inappropriate for entry into this study.

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

США · 2 центра

• University of Chicago Medicine Comprehensive Cancer Center — Chicago
• University of Rochester Medical Center, Wilmot Cancer Center — Rochester

Идентификаторы

NCT: NCT06207123 · IRB23-1382

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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