Trial Outcomes & Findings for Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis (NCT NCT01222260)

Last Updated: 2020-03-30

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2020-03-30

Participant Flow

Between January 2013 and March 2016, 40 patients were enrolled in the study and 31 patients were treated.

Participant milestones

Participant milestones
Measure	Treatment Arm Subjects with relapsed/refractory systemic light-chain (AL) will receive Bendamustine and Dexamethasone. Bendamustine: Patients will start bendamustine at dose level 0 and according to creatinine clearance (CrCl) on day 1 and 2 of each cycle: * CrCl ≥ 60 mL/min: 100 mg/m2 IV on day 1 and 2 of each cycle * CrCl 59 - 30 mL/min: 90 mg/m2 IV on day 1 and 2 of each cycle Available to qualifying subjects is the option to dose escalate to dose level (+)1: * 120 mg/m2 (if CrCl ≥ 60 mL/min at the time of inclusion into the study) * 100 mg/m2 (if CrCl 59-30 mL/min at the time of inclusion into the study) Dexamethasone: 40 mg orally on days 1, 8, 15, 22 of each cycle
Overall Study STARTED	31
Overall Study COMPLETED	29
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Arm n=31 Participants Subjects with AL will receive Bendamustine and Dexamethasone Bendamustine: Patients will start bendamustine at dose level 0 and according to CrCl on day 1 and 2 of each cycle: * CrCl ≥ 60 mL/min: 100 mg/m2 IV on day 1 and 2 of each cycle * CrCl 59 - 30 mL/min: 90 mg/m2 IV on day 1 and 2 of each cycle Available to qualifying subjects is the option to dose escalate to dose level (+)1: * 120 mg/m2 (if CrCl ≥ 60 mL/min at the time of inclusion into the study) * 100 mg/m2 (if CrCl 59-30 mL/min at the time of inclusion into the study) Dexamethasone: 40 mg orally on days 1, 8, 15, 22 of each cycle
Age, Continuous	65 years n=93 Participants
Sex: Female, Male Female	9 Participants n=93 Participants
Sex: Female, Male Male	22 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	3 Participants n=93 Participants
Race (NIH/OMB) White	15 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=93 Participants
Time since diagnosis	31.0 months n=93 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Outcome measures

Outcome measures
Measure	Treatment Arm n=28 Participants Subjects with AL will receive Bendamustine and Dexamethasone Bendamustine: Patients will start bendamustine at dose level 0 and according to CrCl on day 1 and 2 of each cycle: * CrCl ≥ 60 mL/min: 100 mg/m2 IV on day 1 and 2 of each cycle * CrCl 59 - 30 mL/min: 90 mg/m2 IV on day 1 and 2 of each cycle Available to qualifying subjects is the option to dose escalate to dose level (+)1: * 120 mg/m2 (if CrCl ≥ 60 mL/min at the time of inclusion into the study) * 100 mg/m2 (if CrCl 59-30 mL/min at the time of inclusion into the study) Dexamethasone: 40 mg orally on days 1, 8, 15, 22 of each cycle
Partial Hematologic Response (PHR) Rate	16 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment Arm n=28 Participants Subjects with AL will receive Bendamustine and Dexamethasone Bendamustine: Patients will start bendamustine at dose level 0 and according to CrCl on day 1 and 2 of each cycle: * CrCl ≥ 60 mL/min: 100 mg/m2 IV on day 1 and 2 of each cycle * CrCl 59 - 30 mL/min: 90 mg/m2 IV on day 1 and 2 of each cycle Available to qualifying subjects is the option to dose escalate to dose level (+)1: * 120 mg/m2 (if CrCl ≥ 60 mL/min at the time of inclusion into the study) * 100 mg/m2 (if CrCl 59-30 mL/min at the time of inclusion into the study) Dexamethasone: 40 mg orally on days 1, 8, 15, 22 of each cycle
Overall Hematologic Response Rate (OHR)	16 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment Arm n=24 Participants Subjects with AL will receive Bendamustine and Dexamethasone Bendamustine: Patients will start bendamustine at dose level 0 and according to CrCl on day 1 and 2 of each cycle: * CrCl ≥ 60 mL/min: 100 mg/m2 IV on day 1 and 2 of each cycle * CrCl 59 - 30 mL/min: 90 mg/m2 IV on day 1 and 2 of each cycle Available to qualifying subjects is the option to dose escalate to dose level (+)1: * 120 mg/m2 (if CrCl ≥ 60 mL/min at the time of inclusion into the study) * 100 mg/m2 (if CrCl 59-30 mL/min at the time of inclusion into the study) Dexamethasone: 40 mg orally on days 1, 8, 15, 22 of each cycle
Organ Response Rate (ORR)	7 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment Arm n=28 Participants Subjects with AL will receive Bendamustine and Dexamethasone Bendamustine: Patients will start bendamustine at dose level 0 and according to CrCl on day 1 and 2 of each cycle: * CrCl ≥ 60 mL/min: 100 mg/m2 IV on day 1 and 2 of each cycle * CrCl 59 - 30 mL/min: 90 mg/m2 IV on day 1 and 2 of each cycle Available to qualifying subjects is the option to dose escalate to dose level (+)1: * 120 mg/m2 (if CrCl ≥ 60 mL/min at the time of inclusion into the study) * 100 mg/m2 (if CrCl 59-30 mL/min at the time of inclusion into the study) Dexamethasone: 40 mg orally on days 1, 8, 15, 22 of each cycle
Median Overall Survival (OS)	18.2 months Interval 11.3 to 43.8

Adverse Events

Treatment Arm

Serious events: 10 serious events

Other events: 20 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Arm n=29 participants at risk Subjects with AL will receive Bendamustine and Dexamethasone Bendamustine: Patients will start bendamustine at dose level 0 and according to CrCl on day 1 and 2 of each cycle: * CrCl ≥ 60 mL/min: 100 mg/m2 IV on day 1 and 2 of each cycle * CrCl 59 - 30 mL/min: 90 mg/m2 IV on day 1 and 2 of each cycle Available to qualifying subjects is the option to dose escalate to dose level (+)1: * 120 mg/m2 (if CrCl ≥ 60 mL/min at the time of inclusion into the study) * 100 mg/m2 (if CrCl 59-30 mL/min at the time of inclusion into the study) Dexamethasone: 40 mg orally on days 1, 8, 15, 22 of each cycle
General disorders Fatigue	3.4% 1/29 • Number of events 1 • 2 years
Gastrointestinal disorders Diarrhea	3.4% 1/29 • Number of events 1 • 2 years
Renal and urinary disorders Renal dysfunction	6.9% 2/29 • Number of events 2 • 2 years
Infections and infestations Infection	3.4% 1/29 • Number of events 1 • 2 years
Skin and subcutaneous tissue disorders Rash	3.4% 1/29 • Number of events 1 • 2 years
General disorders Infusion-related reaction	3.4% 1/29 • Number of events 1 • 2 years
Infections and infestations Fever and chills	6.9% 2/29 • Number of events 2 • 2 years
Cardiac disorders Atrial fibrillation	3.4% 1/29 • Number of events 1 • 2 years

Other adverse events

Other adverse events
Measure	Treatment Arm n=29 participants at risk Subjects with AL will receive Bendamustine and Dexamethasone Bendamustine: Patients will start bendamustine at dose level 0 and according to CrCl on day 1 and 2 of each cycle: * CrCl ≥ 60 mL/min: 100 mg/m2 IV on day 1 and 2 of each cycle * CrCl 59 - 30 mL/min: 90 mg/m2 IV on day 1 and 2 of each cycle Available to qualifying subjects is the option to dose escalate to dose level (+)1: * 120 mg/m2 (if CrCl ≥ 60 mL/min at the time of inclusion into the study) * 100 mg/m2 (if CrCl 59-30 mL/min at the time of inclusion into the study) Dexamethasone: 40 mg orally on days 1, 8, 15, 22 of each cycle
General disorders Fatigue	27.6% 8/29 • Number of events 8 • 2 years
Blood and lymphatic system disorders Decreased lymphocyte count	20.7% 6/29 • Number of events 6 • 2 years
Renal and urinary disorders Chronic kidney disease	13.8% 4/29 • Number of events 4 • 2 years
General disorders Hypotension	10.3% 3/29 • Number of events 3 • 2 years
General disorders Hypertension	10.3% 3/29 • Number of events 3 • 2 years
Blood and lymphatic system disorders Decreased neutrophil count	10.3% 3/29 • Number of events 3 • 2 years
General disorders Syncope	10.3% 3/29 • Number of events 3 • 2 years
General disorders Nausea	6.9% 2/29 • Number of events 2 • 2 years
Blood and lymphatic system disorders Decreased white blood cell count	6.9% 2/29 • Number of events 2 • 2 years
Blood and lymphatic system disorders Anemia	6.9% 2/29 • Number of events 2 • 2 years

Additional Information

Suzanne Lentzsch, M.D., PhD.

Columbia University Medical Center

Phone: 212-304-5485

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place