Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01222260|
Recruitment Status : Completed
First Posted : October 18, 2010
Results First Posted : March 30, 2020
Last Update Posted : March 30, 2020
|Condition or disease||Intervention/treatment||Phase|
|AL Amyloidosis||Drug: Bendamustine Drug: Dexamethasone||Phase 2|
Systemic light-chain amyloidosis (AL) is a protein conformation disorder due to a clonal plasma cell dyscrasia. There are no established and approved second-line therapies for patients with systemic AL amyloidosis who fail initial melphalan-based treatment, be it high-dose melphalan with stem cell transplant or oral melphalan and dexamethasone (MDex). Therefore new treatments are needed for those who fail initial therapy and for those who initially respond but subsequently relapse.
Therapy of AL is generally based on treatment regimens used in multiple myeloma (MM). Bendamustine achieves partial response with relapsed/refractory MM. Based on this high anti-MM activity, we anticipate that bendamustine will also be very active in clonal plasma cell disorder associated with AL.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of the Combination of Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis|
|Actual Study Start Date :||January 2013|
|Actual Primary Completion Date :||March 2019|
|Actual Study Completion Date :||July 3, 2019|
Experimental: Treatment Arm
Subjects with AL will receive Bendamustine and Dexamethasone
Patients will start bendamustine at dose level 0 and according to CrCl on day 1 and 2 of each cycle:
Available to qualifying subjects is the option to dose escalate to dose level (+)1:
40 mg orally on days 1, 8, 15, 22 of each cycle
Other Name: Decadron
- Partial Hematologic Response (PHR) Rate [ Time Frame: Up to 2 years ]Only patients who have received at least 2 cycles of therapy are eligible for response assessment. The proportion of patients with PHR two months post-treatment will be estimated, with a 95% exact binomial confidence interval. Partial response is defined as the reduction of the difference between involved and uninvolved free light chains (dFLC) of ≥ 50% OR a reduction of ≥ 50% of the M-protein if M-spike is ≥ 0.5 g/dL.
- Overall Hematologic Response Rate (OHR) [ Time Frame: Up to 2 years ]The proportion of response-evaluable patients experiencing OHR will be estimated, with a 95% exact binomial confidence interval. Overall hematologic response rate as defined by normalization of the free light chain levels and ratio, negative serum and urine immunofixation OR reduction in the difference between involved and uninvolved free light chains (dFLC) to <4 mg/dL.
- Organ Response Rate (ORR) [ Time Frame: Up to 2 years ]The proportion of response-evaluable patients experiencing ORR will be estimated, with a 95% exact binomial confidence interval. Amyloid-related organ response will be evaluated on the basis of the accepted criteria described: Kidneys: 30% reduction or drop below 0.5 g in 24-hour urine protein excretion in the absence of progressive renal insufficiency. Heart: N-terminal pro b-type natriuretic peptide (NT-proBNP) or B-type natriuretic peptide response (>30% and >300 ng/L decrease in patients with baseline NT-proBNP ≥ 650 ng/L or New York Heart Association (NYHA) class response (≥ 2 class decrease in subjects with baseline NYHA class 3 or 4). Liver: 50% decrease of an initially elevated alkaline phosphatase level or reduction in the size of the liver by at least 2 cm. Neuropathy: improvement supported by clinical history, neurologic exam, orthostatic vital signs, resolution of severe constipation or reduction of diarrhea to less than 50% of previous movements/day.
- Median Overall Survival (OS) [ Time Frame: Up to 2 years ]Survival is assessed as time to death from first day of treatment The OS function for response-evaluable will be estimated using the product-limit (Kaplan-Meier) estimator, along with 95% confidence bounds. The median survival will be estimated from the survival function. The analysis will be repeated on all patients who receive any therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01222260
|United States, Massachusetts|
|Tufts Medical Center|
|Boston, Massachusetts, United States, 02111|
|Boston Medical Center|
|Boston, Massachusetts, United States, 02118|
|United States, Michigan|
|Barbara Ann Karmanos Cancer Institute|
|Detroit, Michigan, United States, 48201|
|United States, New York|
|Mt. Sinai Medical Center|
|New York, New York, United States, 10023|
|New York, New York, United States, 10032|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Suzanne Lentzsch, MD, PhD||Columbia University|