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
4 other identifiers
interventional
24
1 country
16
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Aug 2022
Longer than P75 for phase_1
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 15, 2021
CompletedFirst Posted
Study publicly available on registry
April 19, 2021
CompletedStudy Start
First participant enrolled
August 3, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2026
May 6, 2026
May 1, 2026
3.9 years
April 15, 2021
May 5, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Incidence of adverse events
Toxicity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Up to 30 days
Maximum tolerated dose
Defined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate.
Up to the end of cycle 1
Recommended phase 2 dose (RP2D)
Will be based on the assessment of toxicities during cycle 1 that meet criteria for dose-limiting toxicities (DLT).
Up to the end of cycle 1
Secondary Outcomes (1)
Overall response rate (complete hematologic response)
After cycles 3, 6, 9, and 12, and every 6 months thereafter up to 2.5 years
Other Outcomes (5)
Expression of BCL-2, BCL-XL, BAX, BAK, BIM, NOXA, and MCL-1
Baseline
Immune profile in the peripheral blood
Before and during treatment
Hematologic response rates
Up to 2.5 years
- +2 more other outcomes
Study Arms (1)
Treatment (venetoclax, ixazomib citrate, dexamethasone)
EXPERIMENTALPatients receive venetoclax PO 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 ECHO during screening and bone marrow biopsy and/or aspiration as well as blood sample collection throughout the study. Patients may undergo CT scans, and/or MRI, and/or PET scans and may optionally undergo urine sample collection throughout the study.
Interventions
Given PO
Undergo ECHO
Given PO
Undergo PET scan
Undergo blood and urine specimen collection
Undergo CT scan
Undergo MRI
Undergo bone marrow aspiration and biopsy
Undergo transabdominal ultrasound
Given PO
Undergo x-ray
Eligibility Criteria
You may qualify if:
- Histologically-proven systemic anti-light chain amyloidosis (AL) confirmed by positive Congo red staining with green birefringence on polarized light microscopy and evidence of a measurable clonal disease that requires active treatment. An underlying plasma cell disorder can be identified by one of the following: clonal plasma cells in the bone marrow (BM), monoclonal protein in the serum or urine, or abnormal free light chain ratio. For patients who are African-American or males \>= 70 years with isolated cardiac involvement, mass spectrometry must be performed to confirm subtyping
- Presence of t(11;14) by fluorescence in situ hybridization (FISH) on bone marrow biopsy, either confirmed at screening or documented with a prior biopsy
- Patient requires therapy, as determined by the treating physician, following at least one line of treatment (No limit on the number of prior treatments)
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of venetoclax in combination with MLN9708 (ixazomib citrate) and dexamethasone in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,000/mcL. Screening absolute neutrophil count (ANC) should be independent of granulocyte- and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for at least 2 weeks
- Platelets \>= 75,000/mcL. Platelet transfusions to help patients meet eligibility criteria are not allowed within 2 weeks before study enrollment
- Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
- Creatinine Calculated clearance \>= 15 mL/min using Cockcroft-Gault equation
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- +25 more criteria
You may not qualify if:
- Patients who have had major surgery or radiotherapy within 14 days prior to entering the study. If the involved radiotherapy field is small, 7 days will be considered a sufficient interval between treatment and administration of the MLN9708 (ixazomib citrate)
- Patients who have had anti-plasma cell therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia
- Patients who are receiving any other investigational agents, within 30 days of the start of this trial and throughout the duration of this trial
- Patients with central nervous system involvement
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to venetoclax, MLN9708 (ixazomib citrate) (including boron or boron-containing products) or dexamethasone
- Strong or moderate CYP3A inhibitors (e.g., erythromycin, ciprofloxacin, diltiazem, fluconazole, verapamil), or strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin, St. John's wort), or moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine) should be avoided
- Venetoclax should be administered using caution with substrates or inhibitors of P-glycoprotein (P-gp)
- Patients with uncontrolled intercurrent illness including, but not limited to: ongoing or active serious or systemic infection (within 14 days prior to study enrollment), active hepatitis B or C virus infection, hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or myocardial infarction (within the past 6 months)
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
- Female patients who are lactating or have a positive serum pregnancy test during the screening period are excluded from this study because MLN9708 (ixazomib citrate) is a proteasome inhibitor with the potential for embryo-lethal effects, and an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with MLN9708 (ixazomib citrate). Patients must stop breastfeeding while on MLN9708 (ixazomib citrate) and until 90 days have passed since their last dose. These potential risks may also apply to other agents used in this study
- Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of MLN9708 (ixazomib citrate), including difficulty swallowing
- Peripheral neuropathy that is \>= grade 3, or grade 2 with pain on clinical examination during the screening period
- Patients that have previously been treated with MLN9708 (ixazomib citrate). Patients who have received prior treatment with venetoclax
- Patients without measurable disease by serum free light chain, serum m-spike or urine monoclonal protein
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (16)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Texas at Austin
Austin, Texas, 78712, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Related Publications (1)
Locke M, Nieto M. AL Amyloidosis: Current Treatment and Outcomes. Adv Hematol. 2025 Mar 3;2025:7280805. doi: 10.1155/ah/7280805. eCollection 2025.
PMID: 40226119DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Michael A Rosenzweig
City of Hope Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 15, 2021
First Posted
April 19, 2021
Study Start
August 3, 2022
Primary Completion (Estimated)
June 30, 2026
Study Completion (Estimated)
June 30, 2026
Last Updated
May 6, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.