Study of ALA-101 in Patients With CD19 Positive Non-Hodgkin Lymphoma and Leukemia.

Официальное название

A Phase 1 Open-Label Dose-Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of ALA-101, Allogeneic, Off-the-shelf, CD19-directed CAR-iNKT Cells in Patients With CD19+ Non-Hodgkin Lymphoma and Leukemia

Обзор

Phase 1 Open-Label Dose-Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of ALA-101

Подробное описание

This is a Phase 1, open-label, dose-escalation and expansion study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary efficacy of ALA-101, an allogeneic, off-the-shelf CD19-directed CAR-iNKT cell therapy, in patients with CD19-positive non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and hairy cell leukemia (HCL).

The dose-escalation phase will assess safety and determine the maximum tolerated dose (MTD). The dose-expansion/backfill phase will further evaluate safety and preliminary efficacy and establish the recommended Phase 2 dose (RP2D).

Study participation includes screening, lymphodepletion, treatment, and follow-up periods. An end-of-study visit will occur at Month 24, after which participants will enter a long-term follow-up study.

Вмешательства

• Препарат ALA-101
  Single IV infusion of ALA-101 post chemotherapy conditioning with Fludarabine and Cyclophosphamide

Первичные конечные точки

• To evaluate the safety and tolerability of ALA-101 in adult participants with CD19+ NonHodgkin Lymphoma (NHL) and CD19+ leukemia [Срок оценки: 2 years]

Вторичные конечные точки (5)

• To determine the maximum tolerated dose (MTD) and appropriate recommended Phase 2 dose (RP2D) for progression into next stages of clinical studies in adult participants with CD19+ NHL and/or CD19+ leukemia. [Срок оценки: 2 years]
• To evaluate the preliminary efficacy of ALA-101 in adult participants with CD19+ NHL and/or CD19+ leukemia [Срок оценки: 2 years]
• To characterize the PK profile of ALA-101 [Срок оценки: 1 year]
• To evaluate the immunogenicity of ALA-101 [Срок оценки: 2 years]
• To characterize the PK profile of ALA-101 [Срок оценки: 1 Year]

Критерии участия

Критерии включения

• Over 18 years old
• Confirmed Diagnoses of Confirmed diagnosis of CD19+ non-Hodgkins lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Marginal Zone Lymphoma, Chronic Lymphatic Leukemia or Hairy Cell Leukemia
• Life Expectancy greater than 3 months
• Adequate Hepatic and Renal Function
• Adequate Bone Marrow Function
• Adequate ECG Vales
• Agree to use appropriate contraception to avoid becoming pregnant for up to 12 months post treatment and agree not to donate sperm or ova for 12 months post treatment

Критерии исключения

• Prior anti-CD1d monoclonal antibody treatment
• Prior allogeneic stem cell transplant except where the participant is greater than 100 days and does not have Graft Versus Host Disease (uncontrolled)
• Prior Organ Transplant
• Previous Malignancy in last 3 years that's active or been treated.
• Current central nervous system involvement by lymphoma or leukaemia
• Evidence of Cardiac Dysfunction
• Active Autoimmune disease requiring systemic immunosuppressive therapy within the past 6 months.
• Known active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.
• History of Graft Vs Host Disease Grade 2 to 4
• No active Graft Vs Host Disease following a minimum of 3 months withdrawal from all Graft Vs Host Disease treatments
• Must not have received systemic anti-cancer therapy for the underlying malignancy within 6 weeks prior to the start of conditioning chemotherapy on Day -6.
• Participants that have received autologous or allogenic CAR-T cell therapy within 3 months prior to commencing screening.
• Use of systemic corticosteroids within 15 days of commencement of conditioning chemotherapy on Day -6 or other immunosuppressive drugs within 30 days
• Recent major surgery (within 4 weeks prior to commencement of conditioning chemotherapy on Day -6) or planned major surgery within 8 weeks following ALA-101 infusion on Day 1.
• Active infection requiring intravenous antibiotic, antifungal, or antiviral medication or hospital admission within 10 days prior to commencement of conditioning chemotherapy on Day -6
• Severe (e.g., severe chronic obstructive pulmonary disease, severe Parkinson's disease) or poorly controlled (e.g., hypertension, diabetes, active inflammatory bowel disease) medical condition.
• Vaccinated with a live vaccine within 28 days prior to commencement of conditioning chemotherapy on Day -6 or planned live vaccination within 6 months following ALA-101 infusion.

Additional criteria apply.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Австралия · 5 центров

• St. Vincent's Hospital — Sydney
• Mater Misericordiae Ltd (MML) — Brisbane
• Royal Adelaide Hospital — Adelaide
• The Alfred Hospital — Melbourne
• Epworth HealthCare — Richmond

Идентификаторы

NCT: NCT07518329 · ALA-101-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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