Teclistamab-Daratumumab in AL Amyloidosis

Официальное название

A Phase 2 Clinical Trial of Teclistamab and Daratumumab in Previously Untreated AL Amyloidosis

Обзор

The purpose of this study is to investigate whether teclistamab-daratumumab combination is effective and safe in AL amyloidosis. The study treatment is divided into cycles (C) and each cycle is 28 days (D). Study treatment is expected to last 6 months.

Подробное описание

The purpose of this study is to assess the effectiveness and safety of teclistamab-daratumumab combination in newly diagnosed AL amyloidosis. The study aims to evaluate whether this combination is able to effectively decrease the level of toxic amyloid-producing light chains circulating in the participants' blood, with the overarching goal of avoiding organ damage, improving organ function, and prolonging life.

Вмешательства

• Препарат Teclistamab
  Teclistamab is a T-cell redirecting bispecific antibody (BsAb) targeting CD3 on T-cells and B-cell maturation antigen (BCMA) on plasma cells.
• Препарат Daratumumab and Hyaluronidase-fihj
  Daratumumab is an monoclonal antibody that targets the CD38 protein on the surface of myeloma cells.

Первичные конечные точки

• Hematologic Complete Response (Heme-CR) rate [Срок оценки: 6 months from treatment initiation]

Вторичные конечные точки (12)

• Minimal Residual Disease (MRD) negativity rate by Free Light Chain Mass Spectrometry (FLC-MS) in serum [Срок оценки: 1 month, 3 months, 6 months, and 18 months]
• MRD-negativity rate by multiparameter flow cytometry (MFC) in bone marrow [Срок оценки: 6 months and 18 months]
• Time to heme-CR [Срок оценки: Day 1 of each cycle, and every 6 weeks after treatment cessation (up to 1 year)]
• Major organ deterioration-progression-free survival (MOD-PFS) rate [Срок оценки: From Cycle 2 to Cycle 6 Day 1 (Each cycle is 28 days), End of treatment visit (up to 6 months from treatment initiation), and up to 18 months from treatment initiation]
• Overall survival rate [Срок оценки: Through study completion, up to 18 months from treatment initiation]
• Frequency of Cytokine Release Syndrome (CRS) [Срок оценки: Throughout Cycle 1 (each cycle is 28 days), Day 0, Day 1, Day 3, Day 8, Day 15, Day 22; Throughout Cycle 2 and Cycle 6 on Day 1 and Day 15; End of treatment visit (up to 6 months from treatment initiation), Post treatment follow-up (up to 18 months)]
• Rate of infections [Срок оценки: Throughout Cycle 1 (each cycle is 28 days), Day 0, Day 1, Day 3, Day 8, Day 15, Day 22; Throughout Cycle 2 and Cycle 6 on Day 1 and Day 15; End of treatment visit (up to 6 months from treatment initiation), Post treatment follow-up (up to 18 months)]
• Number of participants with a heart response after treatment [Срок оценки: 6 months and 18 months]
• Number of No Responses in the heart after treatment [Срок оценки: 6 months and 18 months]
• Number of Partial Responses (PR) in participants who experienced a heart response after treatment [Срок оценки: 6 months and 18 months]
• Number of Very Good Partial Responses (VGPR) in participants who experienced a heart response after treatment [Срок оценки: 6 months and 18 months]
• Number of Complete Response (CR) in participants who experienced a heart response after treatment [Срок оценки: 6 months and 18 months]

Критерии участия

Критерии включения

• Age >18 years and able to sign Informed Consent Form (ICF). If the individual being considered for participation in this study is unable to provide informed consent due to medical, cognitive, or other conditions, a legally authorized representative (LAR) may consent on their behalf.
• Ability to comply with the study protocol, in the investigator's judgment.
• Confirmed histopathological diagnosis of systemic AL amyloidosis by mass spectrometry or immunohistochemistry (IHC) or Immunofluorescence (IF) on a tissue biopsy that is positive for Congo Red.
• Patient must not have received any prior plasma cell clone-directed therapy.
• Measurable hematologic disease, defined as one of the following:

• Difference between involved and uninvolved serum free light chain (dFLC) ≥50 mg/L and/or 5 mg/dL
• Serum M-protein ≥0.5 g/dL on protein electrophoresis
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• One or more organs involved by AL amyloidosis as per consensus guidelines
• Pre-treatment clinical laboratory values meeting the following criteria during the screening phase:

• Absolute neutrophil count ≥0.75 × 10\^9/L
• Hemoglobin level ≥8.0 g/dL; red blood cell transfusion allowed until 7 days before C1D0.
• Platelet count ≥50 × 10\^9/L; Platelet transfusions are acceptable without restriction during the Screening period
• Alanine aminotransferase level (ALT) ≤2.5 times the Upper Limit of Normal (ULN)
• Aspartate aminotransferase (AST) ≤2.5 times the ULN
• Total bilirubin level ≤1.5 × ULN except for subjects with Gilbert syndrome, in which case direct bilirubin ≤2 × ULN
• Estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m\^2, measured by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs.

For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm.

Критерии исключения

• Prior therapy for AL amyloidosis or multiple myeloma with the exception of 160 mg dexamethasone (or equivalent corticosteroid) maximum exposure prior to C1D0.
• Patients meeting criteria for symptomatic multiple myeloma by any one of the following: (a) Lytic lesions on imaging (Skeletal survey, whole body CT or MRI, or PET/CT) (b) Plasmacytoma, (c) Hypercalcemia without any alternate etiology, (d) Bone marrow plasma cell infiltrate of greater than 60%.

Patients with involved/uninvolved serum FLC ratio>100 as the sole myeloma-defining event will be allowed.

• Evidence of significant cardiovascular conditions as specified below:

• NT-Pro BNP > 8500 pg/mL, and/or
• NYHA Class IIIb or IV functional class
• History of other malignancy that could affect compliance with the protocol or interpretation of results.

Patients with a history of curatively treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, breast cancer, or Hodgkin's Lymphoma are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will be excluded, unless the malignancy has been in remission without treatment for ≥ 2 years prior to enrollment.

• Evidence of other clinically significant uncontrolled condition(s) including, but not limited to, uncontrolled systemic infection (viral, bacterial, or fungal).
• Patients on renal replacement therapy
• Patients with HIV who are not on HAART or those with active hepatitis A, B, or C infection.
• Planned stem cell transplant during the first 6 cycles of protocol therapy are excluded. Stem cell collection during the first 6 cycles of protocol therapy is permitted, as per investigators' discretion.
• Known hypersensitivity to any of the agents
• Patients who are receiving any other investigational agent concurrently.

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 · 3 центра

• Boston Medical Center — Boston
• Columbia University Irving Medical Center — New York
• Medical College of Wisconsin — Milwaukee

Идентификаторы

NCT: NCT07110844 · AAAV8827 · 1452862

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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