AL AmyloidosisPhase 2NCT01222260
Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis
A Phase 2 study testing Bendamustine and Dexamethasone in people with AL Amyloidosis, run by Columbia University at 6 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AL Amyloidosis
- What is being tested?
- Bendamustine and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 6 sitesUnited States
- Study dates
- Jan 2013to 3 Jul 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 20Show fewer
- 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)
- Calculated creatinine clearance (CrCl) greater than or equal to 30 mL/min (Cockcroft-Gault Formula )
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN)
- Serum bilirubin <1.5 x ULN
- Serum potassium within normal limits
- Total serum calcium (corrected for serum albumin) or ionized calcium ≤ ULN
Who cannot join
- 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)
Show all 13Show fewer
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Tufts Medical Center
Boston, Massachusetts, 02111
Boston Medical Center
Boston, Massachusetts, 02118
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
Mt. Sinai Medical Center
New York, New York, 10023
Columbia University
New York, New York, 10032
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase II Study of the Combination of Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis
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).
Read the detailed description
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.
- Conditions
- AL Amyloidosis
- Being tested
- Bendamustine, Dexamethasone
- Keywords
- Amyloidosis, Dexamethasone, Bendamustine, Relapsed AL Amyloidosis
- Medical subject headings
- Immunoglobulin Light-chain Amyloidosis, Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BendamustineDrug
Also called Bendamustine Hydrochloride, Treanda ®
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)
DexamethasoneDrug
Also called Decadron
40 mg orally on days 1, 8, 15, 22 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Subjects with AL will receive Bendamustine and Dexamethasone Receives: Drug: Bendamustine; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 2 years
Secondary outcomes (3)
Overall Hematologic Response Rate (OHR)
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.
Measured: Up to 2 years
Organ Response Rate (ORR)
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.
Measured: Up to 2 years
Median Overall Survival (OS)
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.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2010 (estimated)
- Study startJan 2013
- Primary completionMar 2019
- Study completion3 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AL AmyloidosisStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Cephalon
- Responsible party
- Principal investigator, Suzanne Lentzsch, MD, Columbia University
- Investigators
- Suzanne Lentzsch, MD, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01222260
- Sponsor's protocol ID
- AAAJ7800
- Other IDs
- 10-012 (PRO10050217)
- Status last verified
- Mar 2020
- First submitted
- 14 Oct 2010
- Last updated
- 30 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 32083996
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of the Combination of Bendamustine and Dexamethasone in Patients With Relapsed AL Amyloidosis
- ClinicalTrials.gov ID
- NCT01222260
- Acronym / sponsor ID
- AAAJ7800
- Conditions
- AL Amyloidosis
- Keywords
- Amyloidosis, Dexamethasone, Bendamustine, Relapsed AL Amyloidosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Cephalon
- Study start
- Jan 2013 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- 3 Jul 2019 (actual)
- First posted
- 18 Oct 2010 (estimated)
- Results
- Posted 30 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Drug: Bendamustine, Drug: DexamethasoneSubjects with AL will receive Bendamustine and Dexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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:
- 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
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BendamustineAlso: Bendamustine Hydrochloride, Treanda ®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) | Drug | Treatment Arm |
| DexamethasoneAlso: Decadron40 mg orally on days 1, 8, 15, 22 of each cycle | Drug | Treatment Arm |
Primary outcome
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.
3 secondary outcomes
Overall Hematologic Response Rate (OHR)
Time frame: Up to 2 years
Organ Response Rate (ORR)
Time frame: Up to 2 years
Median Overall Survival (OS)
Time frame: Up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32083996Lentzsch 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.
- Individual participant dataSharing planned: Yes. 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.
Related trials for AL Amyloidosis
RecruitingPhase 1
Study of GC012F, CAR-T Therapy Targeting CD19 and BCMA in Chinese Participants With Relapsed or Refractory AL Amyloidosis
Relapsed/Refractory AL Amyloidosis
RecruitingObservational study
Essen Amyloidosis Registry
Amyloidosis; Systemic, Amyloidosis Cardiac
Active, not recruitingPhase 2
Siltuximab to Decrease Symptom Burden After Autologous Stem Cell Transplantation for Patients With Multiple Myeloma and AL Amyloidosis
Multiple Myeloma, AL Amyloidosis
RecruitingPhase 2
Study of HBI0101 (NXC-201) CAR-T Therapy in Multiple Myeloma and Light-Chain Amyloidosis
Multiple Myeloma, Refractory to Standard Treatment, Multiple Myeloma, Relapsed
RecruitingPhase 2
A Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Cyclophosphamide, Bortezomib, and Dexamethasone in Adult Participants With Newly Diagnosed Amyloid Light Chain (AL) Amyloidosis
Amyloidosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suzanne Lentzsch, MD, PhD principal investigator
Columbia University
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bendamustine and Dexamethasone in people with AL Amyloidosis, run by Columbia University at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Partial Hematologic Response (PHR) Rate (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01222260, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2020.