Trial of Venetoclax (ABT-199) and Dexamethasone for Relapsed or Refractory Systemic AL Amyloidosis
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|ClinicalTrials.gov Identifier: NCT03000660|
Recruitment Status : Suspended (partial clinical hold per FDA)
First Posted : December 22, 2016
Last Update Posted : May 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|AL Amyloidosis||Drug: Venetoclax Drug: Dexamethasone||Phase 1|
The study is being conducted to determine the safety, tolerability and maximum tolerated dose of Venetoclax and dexamethasone in relapsed or refractory amyloid light chain (AL) amyloidosis patients. AL amyloidosis is a disease involving cells called plasma cells that make antibodies as part of your immune system. These cells are not functioning the way they are supposed to and they start to produce abnormal fragments of antibodies that are toxic to your body and can form amyloid. The antibody fragments are called "light chains." They can cause damage to organs, especially the kidneys, heart, skin, liver, and lungs.
Researchers are looking for ways to stop the light chains from being formed to treat the disease. Under some circumstances, patients will receive chemotherapy drugs in order to manage the disease. However, researchers do not know what the best treatment is for relapsed AL amyloidosis, so the researchers are testing new drugs or new combinations of drugs to see what will work best with the least side effects.
The researchers want to find out if Venetoclax (ABT-199) in addition to dexamethasone will reduce or eliminate AL amyloidosis plasma cells. In this study, varying doses of Venetoclax will be given to determine the maximum tolerated and safe dose for further study. The researchers may also gain a better understanding of whether Venetoclax and dexamethasone can counter the plasma cell disease that causes AL amyloidosis.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Venetoclax (ABT-199) and Dexamethasone for Relapsed or Refractory Systemic AL Amyloidosis|
|Study Start Date :||January 2017|
|Estimated Primary Completion Date :||January 2020|
|Estimated Study Completion Date :||January 2021|
Experimental: Venetoclax and Dexamethasone
Venetoclax will be given at one of four escalating doses (100 mg/day, 200 mg/day, 400 mg/day, or 800 mg/day) by mouth on each day of the cycle. Dexamethasone will be given at 20mg by mouth on days 1, 8, 15, and 22 of each cycle.
Venetoclax at one of four escalating doses
Other Name: ABT-199
Dexamethasone 20mg by mouth on days 1, 8, 15, and 22 of each cycle.
- Participants with treatment related adverse events using NCI CTCAE version 4.03. [ Time Frame: Up to 8 months after beginning study drug ]Dose limiting toxicity will be based on hematologic and non-hematologic adverse events that are considered by the investigator to be possibly related to Venetoclax include any Grade 4 thrombocytopenia lasting more than 7 days, any Grade 4 neutropenia lasting more than 7 days, any Grade 3 or higher nonhematologic toxicity, a delay of more than 2 weeks in the initiation of Cycle 2 of treatment because of a lack of adequate recovery of Venetoclax-related hematological or nonhematologic toxicities, and any other Venetoclax-related nonhematologic toxicities Grade 2 or greater than, in the opinion of the investigator, requires discontinuation of therapy with Venetoclax. Also, events of concern that may be related to Venetoclax therapy will include worsening neuropathy, ventricular or atrial arrhythmia with hemodynamic instability, fluid retention that does not resolve with 3 or 4 days of intravenous diuretic therapy and bedrest, symptomatic congestive heart failure, and hypotension.
- Hematologic response based on serum free light chain (FLC) response criteria. [ Time Frame: Up to 8 months after beginning study drug ]Complete response is normalization of FLC levels and ratio with negative immunofixation studies of serum and urine. Very good partial response is reduction of the difference between the involved and uninvolved FLC to less than 40mg/L. Partial response is reduction of the difference between involved and uninvolved FLC of greater than 50% baseline. No response or stable disease is none of the above.
- Proportion of subjects with progression-free survival [ Time Frame: Until disease progression up to three (3) years ]Hematologic progression will be evaluated every 12 weeks until the subject progresses. From CR any detectable monoclonal protein or abnormal free light chain ratio (light chain must double). From PR, 50% increase in serum M-protein of > 0.5 g/dl or 50% increase in urine M-protein to > 200 mg/day (a visible peak must be present), or free light chain increase of 50% to > 100 mg/L
- Overall survival of subjects [ Time Frame: From time of end of treatment to death for up to three (3) years ]Subjects will be followed until death after they have come off study
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03000660
|United States, Massachusetts|
|Tufts Medical Center|
|Boston, Massachusetts, United States, 02111|
|Principal Investigator:||Raymond Comenzo, MD||Tufts Medical Center|