Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis

NCT01222260 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: AAAJ780010-012 (PRO10050217)
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

Brief Summary

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).

Conditions

AL Amyloidosis

Keywords

Amyloidosis; Dexamethasone; Bendamustine; Relapsed AL Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Partial Hematologic Response (PHR) Rate

  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.

  Up to 2 years

Secondary Outcomes (3)

• Overall Hematologic Response Rate (OHR)

  Up to 2 years

• Organ Response Rate (ORR)

  Up to 2 years

• Median Overall Survival (OS)

  Up to 2 years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Subjects with AL will receive Bendamustine and Dexamethasone

Drug: Bendamustine; Drug: Dexamethasone

Interventions

Bendamustine DRUG

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)

Also known as: Bendamustine Hydrochloride, Treanda ®

Treatment Arm

Dexamethasone DRUG

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

Also known as: Decadron

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged ≥ 18 years old
• Histopathology of amyloidosis or light chain deposition disease based on detection by polarizing microscopy of green bi-refringent material in Congo red-stained tissue specimens or characteristic electron microscopy appearance or immunohistochemical stain with anti-light chain anti-sera
• Demonstrate measurable disease as defined by one or more of the following:
• Serum monoclonal protein ≥ 0.5 g/dL by serum electrophoresis
• Urine monoclonal protein \> 200 mg/dL in a 24 hr urine electrophoresis
• Serum immunoglobulin free light chain ≥ 5 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio. The difference between involved and uninvolved free light chains should be ≥ 5 mg/dL (dFLC)
• Demonstrate clonal population of plasma cells in the bone marrow or immunohistochemical stain with anti-light chain anti-sera of amyloid fibrils
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Patients had at least one prior regimen consisting of at least 1 cycle
• If not previously transplanted, patient should be either ineligible for autologous stem cell transplantation (ASCT), or must have declined the option of ASCT. Patients who have previously had ASCT and have subsequently progressed are eligible, provided other entry criteria are met
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Patients must meet the following laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Hemoglobin ≥ 9 g/dl (May transfuse packed red blood cells (PRBC) to meet parameter)
• Platelets ≥ 100x 10\^9/L (Must be independent of platelet transfusion)

You may not qualify if:

• Patients meeting the criteria for symptomatic MM:
• Lytic lesions on skeletal survey or plasmacytoma
• Patients meeting International Myeloma Working Group definition of symptomatic myeloma with symptoms only related to associated amyloidosis who would otherwise only meet the criteria for smoldering MM are potentially eligible
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or
• electrocardiographic evidence of acute ischemia or active conduction system abnormalities (not including 1st degree atrioventricular (AV)-block, Wenckebach type 2nd degree heart block, or left bundle branch block. Prior to study entry, any electrocardiogram (ECG) abnormality at Screening has to be documented by the investigator or an authorized physician sub-investigator as not medically relevant). Note: There is no lower limit of left ventricular ejection fraction below which patients are excluded from participation.
• Patients with N-terminal (NT)-proBNP ≥ 1800nb/L or B-type natriuretic peptide (BNP) ≥ 400 ng/L, abnormal cardiac troponin T (cTnT) or cardiac troponin l (cTnI)
• Patient has received other investigational drugs within 14 days prior to enrollment
• Any form of secondary / familial amyloidosis
• Serious concurrent illness, which in the opinion of the investigator or an authorized physician sub-investigator would interfere with participation in this clinical study,
• Known HIV infection.
• Inability to provide informed consent or to comply with the schedule of office and treatment visits
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women(woman not of child-bearing potential is defined as any woman whose menstrual periods have stopped in the past 12 consecutive months or have had a complete hysterectomy or both ovaries surgically removed).
• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, low-risk prostate cancer, or cancer after curative treatment.

Sponsors & Collaborators

• Columbia University: lead
• Cephalon: collaborator

Study Sites (6)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mt. Sinai Medical Center

New York, New York, 10023, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Lentzsch S, Lagos GG, Comenzo RL, Zonder JA, Osman K, Pan S, Bhutani D, Pregja S, Sanchorawala V, Landau H. Bendamustine With Dexamethasone in Relapsed/Refractory Systemic Light-Chain Amyloidosis: Results of a Phase II Study. J Clin Oncol. 2020 May 1;38(13):1455-1462. doi: 10.1200/JCO.19.01721. Epub 2020 Feb 21.

  PMID: 32083996 DERIVED

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis; Amyloidosis

Interventions

Bendamustine Hydrochloride; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Suzanne Lentzsch, M.D., PhD.
• Organization: Columbia University Medical Center

sl3440@cumc.columbia.edu

212-304-5485

Study Officials

• Suzanne Lentzsch, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical Medicine

Study Record Dates

• First Submitted: October 14, 2010
• First Posted: October 18, 2010
• Study Start: January 1, 2013
• Primary Completion: March 1, 2019
• Study Completion: July 3, 2019
• Last Updated: March 30, 2020
• Results First Posted: March 30, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 3 months after manuscript publication for a period of 5 years after the publication.
• Access Criteria: Proposals for access should be sent to cancerclinicaltrials@cumc.columbia.edu.

Locations

US (6)