Venetoclax, MLN9708 (Ixazomib Citrate) and Dexamethasone for the Treatment of Relapsed or Refractory Light Chain Amyloidosis : A Phase 1/1a Study of Venetoclax, MLN9708 (Ixazomib Citrate) and Dexamethasone for Relapsed/Refractory Light Chain Amyloidosis

PRIMARY OBJECTIVES:I. To evaluate the safety and tolerability of venetoclax, MLN9708 (ixazomib citrate), and dexamethasone when used in combination.II. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of venetoclax, MLN9708 (ixazomib citrate), and dexamethasone when used in combination.SECONDARY OBJECTIVES:I. To observe and record anti-tumor activity. II. To obtain a preliminary estimate of the anti-light chain amyloidosis (AL) activity as assessed by incidence of complete hematologic response (CR) and overall hematologic response (partial response [PR], very good partial response [VGPR], and CR).III. To estimate the organ-specific response rates, among patients with measurable organ disease, using standard criteria.IV. To estimate progression free survival.EXPLORATORY OBJECTIVES:I. To evaluate expression of BCL-2, BCL-XL, and MCL-1 on the surface of plasma cells of patients with AL.II. To describe the immune profile in the peripheral blood of patients with AL before and during treatment with venetoclax, MLN9708 (ixazomib citrate), and dexamethasone at multiple time points.III. To estimate hematologic response rates using mass spectrometry to detect persistence of a monoclonal protein in the serum and urine.IV. To characterize the genotype of the CD138+ plasma cell in patients with AL and t(11;14) and compare findings to those of patients with multiple myeloma and t(11;14) as reported in prior studies.V. To determine presence of minimal residual disease by Next Generation Sequencing (NGS) in patients achieving a hematologic CR.OUTLINE: This is a dose-escalation study of venetoclax and ixazomib citrate.Patients receive venetoclax orally (PO) once daily (QD) on days 1-28, ixazomib citrate PO on days 1, 8 and 15, and dexamethasone PO on days 1, 8, 15 and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may undergo x-ray imaging and abdominal ultrasound during screening. Patients undergo bone marrow biopsy and/or aspiration as well as blood sample collection throughout the study. Patients may undergo computed tomography (CT) scans, and/or magnetic resonance imaging (MRI), and/or positron emission tomography (PET) scans throughout the study.After completion of study treatment, patients are followed every 1-3 months until disease progression or death..

Medienart:	Klinische Studie

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	ClinicalTrials.gov - (2024) vom: 20. März Zur Gesamtaufnahme - year:2024

Sprache:	Englisch

Links:	Volltext [kostenfrei]

Themen:	610 Amyloidosis Immunoglobulin Light-chain Amyloidosis Phase: Phase 1 Recruitment Status: Recruiting Study Type: Interventional

Anmerkungen:	Source: Link to the current ClinicalTrials.gov record., First posted: April 19, 2021, Last downloaded: ClinicalTrials.gov processed this data on March 27, 2024, Last updated: March 27, 2024

Study ID:	NCT04847453 NCI-2021-03038 PHI-124 10440 UM1CA186717
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PPN (Katalog-ID):	CTG000034444