NCT04847453

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/Ia trial finds the best dose and side effects of venetoclax given in combination with ixazomib citrate and dexamethasone in treating patients with light chain amyloidosis that has come back (relapsed) or does not respond to treatment (refractory) and who have an abnormal genetic change \[translocation t(11;14)\]. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Ixazomib citrate is in a class of medications called proteasome inhibitors. It works by helping to kill cancer cells. Anti-inflammatory drugs such as dexamethasone reduce inflammation by lowering the body's immune response and are used with other drugs in the treatment of some types of cancer. Combination therapy with venetoclax, ixazomib citrate and dexamethasone may be effective in treatment of relapsed or refractory light chain amyloidosis.

Detailed description

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 of each cycle. 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 echocardiography (ECHO) during screening and 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 and may optionally undergo urine sample collection throughout the study. After completion of study treatment, patients are followed every 1-3 months until disease progression or death.

Conditions

• Recurrent AL Amyloidosis
• Refractory AL Amyloidosis

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood and urine specimen collection
PROCEDURE	Bone Marrow Aspiration and Biopsy	Undergo bone marrow aspiration and biopsy
PROCEDURE	Computed Tomography	Undergo CT scan
DRUG	Dexamethasone	Given PO
PROCEDURE	Echocardiography Test	Undergo ECHO
DRUG	Ixazomib Citrate	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Positron Emission Tomography	Undergo PET scan
PROCEDURE	Transabdominal Ultrasound	Undergo transabdominal ultrasound
DRUG	Venetoclax	Given PO
PROCEDURE	X-Ray Imaging	Undergo x-ray

Timeline

• Start date: 2022-08-03
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2021-04-19
• Last updated: 2026-04-13

Locations

16 sites across 1 country: United States

Regulatory

• FDA-regulated drug study