Nutritional and Metabolic Diseases

All Conditions

Neoplasms

Immune System Diseases

Blood and Lymph Conditions

Rare Diseases

Amyloidosis

Immunoglobulin Light-chain Amyloidosis

Proteostasis Deficiencies

Metabolic Diseases

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Immunoproliferative Disorders

Paraproteinemias

AL Amyloidosis

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Bendamustine Hydrochloride

Dexamethasone acetate

BB 1101

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antineoplastic Agents, Alkylating

Alkylating Agents

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:

* 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)

Bendamustine

40 mg orally on days 1, 8, 15, 22 of each cycle

Suzanne Lentzsch, MD, PhD

The study is being done to see if the combination of bendamustine and dexamethasone will help people with amyloidosis that has returned after standard treatment, and to to estimate the partial hematologic response rate (PHR).

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.

Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis

Phase II Study of the Combination of Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis

Deidentified individual participant data that underlie the reported results will be made available 3 months after publication for a period of 5 years after the publication.

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.

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.

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.

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.

Cephalon

Columbia University

Associate Professor of Clinical Medicine

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

Treatment Arm

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Time since diagnosis

Suzanne Lentzsch, M.D., PhD.

Partial Hematologic Response (PHR) Rate

Overall Hematologic Response Rate (OHR)

Organ Response Rate (ORR)

Median Overall Survival (OS)

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

Spots Global Cancer Trial Database for Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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