Venetoclax, Ixazomib, and Dexamethasone for Relapsed/Refractory AL Amyloidosis
This study is testing a combination of three drugs: venetoclax, ixazomib citrate, and dexamethasone. It's for people with light chain amyloidosis (AL amyloidosis) that has returned (relapsed) or isn't responding to other treatments (refractory), especially if you have a specific genetic change called translocation t(11;14). Venetoclax works by blocking a protein called BCL-2, which helps cancer cells survive. Ixazomib citrate helps kill cancer cells. Researchers want to find the safest and most effective dose of these drugs together and understand their side effects. They will also look at how well the treatment shrinks the amyloidosis. This study plans to enroll 24 participants.
- Study design
- This is an interventional study, meaning you will receive a specific treatment. It is a Phase 1/1a trial, which typically involves a small number of participants to find the best dose and side effects.
- What's involved
- You would undergo blood and urine collection, bone marrow aspiration and biopsy, CT scans, and echocardiogram (ECHO) tests. Dexamethasone is given by mouth (PO).
- Compensation
- Not stated in the trial record.
- Follow-up
- The incidence of adverse events will be measured up to 30 days after treatment. Other endpoints are measured up to the end of cycle 1.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04847453
Venetoclax, MLN9708 (Ixazomib Citrate) and Dexamethasone for the Treatment of Relapsed or Refractory Light Chain Amyloidosis
Active, Not Recruiting
PHASE1Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~24 participants
Updated 2026-07-31 on ClinicalTrials.gov
What's tested:Biospecimen CollectionBone Marrow Aspiration and BiopsyComputed TomographyDexamethasoneEchocardiography TestIxazomib Citrate
At a glance
Recruiting sites
0 of 16 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Incidence of adverse events
Measured over Up to 30 days
+2 more outcomes measured
Conditions
Where it's being run
16 sites across 11 statesNew York3
California2
Massachusetts2
Virginia2
Georgia1
Maryland1
North Carolina1
Ohio1
Study leadership
- Michael A Rosenzweig · PRINCIPAL_INVESTIGATOR · City of Hope Comprehensive Cancer Center LAO
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
AL Amyloidosis Cardiac Risk stage I, II or IIIa disease based on the 2013 European Modification of the 2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement (Dispenzieri et al., 2004; Wechalekar et al., 2013)
Staging system defined by: NT-proBNP cut off of \< 332 pg/mL and troponin I cut-off of \< 0.10 ng/mL (in the absence of troponin T, troponin I \>= 0.1 ng/mL can be used) as thresholds for stages I, II and III; NT-proBNP =\< 8500 pg/ml for stage IIIa
Stage I, both under threshold;
Stage I: Zero markers above threshold: NT-proBNP \< 332 ng/L AND troponin T (TnT) =\< 0.035 ng/mL; NT-proBNP \< 332 ng/L AND TnI =\< 0.1 ng/mL
Stage II, either troponin or NT-proBNP (but not both) over threshold;
Stage II: One marker above threshold: NT-proBNP \>= 332 ng/L OR TnT \>= 0.035 ng/mL; NT-proBNP \>= 332 ng/L OR TnI \>= 0.1 ng/mL
Stage III, both over threshold;
Stage IIIa, both over threshold but NT-proBNP =\< 8500 pg/ml
Stage IIIa: Two markers above threshold: NT-proBNP \>= 332 ng/L BUT =\< 8,500 ng/L AND TnT \>= 0.035 ng/mL; NT-proBNP \>= 332 ng/L BUT =\< 8,500 ng/L AND TnI \>= 0.1 ng/mL
Stage IIIb: Two markers above threshold: NT-proBNP \> 8,500 ng/L AND TnT \>= 0.035 ng/mL; NT-proBNP \> 8,500 ng/L AND TnI \>= 0.1 ng/mL
Life expectancy \>= 3 months
Plasma cell burden =\< 60%
Absence of bone lesions and other end organ disease consistent with multiple myeloma (patients with plasma cell burden between 10 and 60% without end organ disease can be included)
Measurable disease of AL amyloidosis as defined by at least one of the following: 1) serum or urine monoclonal protein \>= 500 mg/dL by protein electrophoresis, or 2) serum free light chain \>= 20 mg/L with an abnormal kappa:lambda ratio or the difference between involved and uninvolved free light chains (dFLC) \>= 20 mg/L
It is not known what effects MLN9708 (ixazomib citrate), venetoclax, and dexamethasone have on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Nonsterilized female patients of reproductive age group and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below.
Female patients must meet 1 of the following:
Postmenopausal for at least 1 year before the screening visit, or
Surgically sterile, or
If they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing of the informed consent form through 90 days after the last dose of study drug, or
Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception)
Male patients, even if surgically sterilized (i.e., status postvasectomy) must agree to 1 of the following:
Practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, or
Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner\] and withdrawal are not acceptable methods of contraception)
Left ventricular ejection fraction \>= 35% by echocardiogram.
Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible
Exclusion
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
Patients with New York Heart Association classification III/IV. Patients with advanced cardiac amyloidosis, Mayo stage IIIB based on European Modification of the 2004 Standard Mayo Clinic Staging in patients with advanced cardiac involvement with NT-Pro BNP \> 8500 pg/mL (Wechalekar et al., 2013)
Patients with grade 3 or worse diarrhea
What this trial measures
- Incidence of adverse eventsUp to 30 days
Toxicity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
- Maximum tolerated doseUp to the end of cycle 1
Defined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate.
- Recommended phase 2 dose (RP2D)Up to the end of cycle 1
Will be based on the assessment of toxicities during cycle 1 that meet criteria for dose-limiting toxicities (DLT).