AmyloidosisPhase 2NCT01083316
Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation for Primary (AL) Amyloidosis
A Phase 2 study testing Bortezomib, Dexamethasone and Melphalan in people with Amyloidosis, run by Boston Medical Center at 1 site in United States.
Trial summary
The drugs dexamethasone and bortezomib are both FDA-approved for the treatment of multiple myeloma, a disease very similar to amyloidosis. However, they are currently investigational for the treatment of amyloidosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyloidosis
- What is being tested?
- Bortezomib, Dexamethasone and Melphalan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2009to 4 Sep 2020
- 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
- Histological diagnosis of primary systemic (AL) amyloidosis based on:
- Deposition of amyloid material by congo red stain showing characteristic green birefringence, and
- monoclonal light chain protein in the serum or urine or immunohistochemical studies or serum free light chain assay and
- evidence of tissue involvement other than carpal tunnel syndrome, i.e. positive immunohistochemical staining of bone marrow demonstrating clonal plasma cells; or tissue amyloid deposits with anti-kappa or anti-lambda anti-serum; evidence for a plasma cell dyscrasia (PCD) by serum/urine or bone marrow; or overwhelmingly convincing clinical features e.g. macroglossia, associated with other systemic manifestations.
- Note: Patients with senile, secondary, localized, dialysis-related or familial amyloidosis are not eligible. Confirmation of tissue diagnosis at all sites of organ dysfunction is encouraged, but not required.
- Must be at least 18 years of age.
Show all 13Show fewer
- Must have a performance status of 0-2 by Southwest Oncology Group criteria
- Must have left ventricular ejection fraction (LVEF) at least 45% by echocardiogram within 60 days of enrollment
- Prior chemotherapy with alkylating agent allowed only if no evidence of Myelodysplastic Dysplastic Syndrome (MDS) morphologically or cytogenetically. Total cumulative dose of oral melphalan must be less than 300 mg. Patients should not have received any cytotoxic therapy less than 4 weeks prior to registration and should have fully recovered from the effects of such therapy.
- Pulmonary Function Tests must show Diffusing capacity of the lungs for carbon monoxide (DLCO) at least 50%.
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
Who cannot join
- No overt multiple myeloma (over 30% bone marrow plasmacytosis, extensive (great than 2) lytic lesions, hypercalcemia).
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 3 years.
- No known to be HIV positive.
- No platelet count of less than or equal to 70,000 within 14 days before enrollment.
- No absolute neutrophil count of less than or equal to 1000 within 14 days before enrollment.
- No greater than or equal to Grade 2 peripheral neuropathy within 14 days before enrollment.
Show all 11Show fewer
- No myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- No hypersensitivity to bortezomib, boron or mannitol.
- No pregnant or breast-feeding females. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Must not have received other investigational drugs with 14 days before enrollment
- No serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial of Induction Therapy With Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation in Patients With AL Amyloidosis
The drugs dexamethasone and bortezomib are both FDA-approved for the treatment of multiple myeloma, a disease very similar to amyloidosis. However, they are currently investigational for the treatment of amyloidosis.
We want to find out if the addition of dexamethasone and bortezomib to standard high dose chemotherapy and stem cell transplant can help improve response.
Read more
Standard treatment includes four steps: 1) Stem Cell Mobilization (standard) 2) Stem Cell Collection (standard) 3) Conditioning Regimen (Melphalan chemotherapy). The conditioning regimen helps to kill the abnormal cells in the body and makes room in the bone marrow for new blood stem cells to grow. 4) Stem Cell Infusion
Participants in this study will have an additional treatment step called "induction therapy", designed as the first step towards reducing the number of abnormal cells in the body. Two cycles of the investigational drugs bortezomib and dexamethasone will be given during induction therapy. In addition, bortezomib will given as part of the conditioning regimen, in addition to the standard melphalan chemotherapy.
Read the detailed description
The drugs dexamethasone and bortezomib are both FDA-approved drugs for the treatment of multiple myeloma, a disease very similar to amyloidosis. However, they are currently investigational for the treatment of amyloidosis.
The investigators want to find out if the addition of dexamethasone and bortezomib to standard treatment of high dose chemotherapy and stem cell transplant can help improve response to treatment.
- Conditions
- Amyloidosis
- Being tested
- Bortezomib, Dexamethasone, Melphalan
- Keywords
- Amyloid, Amyloidosis, AL Amyloidosis, Primary Amyloidosis, Stem Cell Transplant
- Medical subject headings
- Amyloidosis, Alzheimer Disease, Immunoglobulin Light-chain Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
Induction:
Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days
Conditioning:
Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4
DexamethasoneDrug
Also called Decadron
Induction:
Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days
MelphalanDrug
Also called Alkeran
Conditioning:
Melphalan 70-100 mg/m2/day IV on days -2 and -1
| Study group | Role | What they receive |
|---|---|---|
| Single Arm - Investigational | Experimental | Induction:
Bortezomib (Velcade) 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days
Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days
Conditioning:
Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4
Melphalan 70-100 mg/m2/day IV on days -2 and -1 Receives: Drug: Bortezomib; Drug: Dexamethasone; Drug: Melphalan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Disease Response
Complete response: Normal serum free light chain ratio and Negative serum and urine immunofixation electrophoresis Very good partial response: Difference in serum free light chains less than 40 mg/L Partial Response: >50% Reduction in the difference in serum free light chains
Measured: One year
Number of Participants Surviving at 100 Days Post Transplant
Measured: 100 days
Number of Participants Proceeding to Transplant Following Induction
Measured: 2 months
Secondary outcomes (1)
Number of Participants Surviving at 5 Years
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2010 (estimated)
- Study startSep 2009
- Primary completionAug 2013
- Study completion4 Sep 2020
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.
- Other trials for AmyloidosisStudies of the same condition, open and under way.
- More trials run by Boston Medical CenterThe 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
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Vaishali Sanchorawala, MD, Principal investigator, Boston Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01083316
- Sponsor's protocol ID
- H-28441
- Other IDs
- X05292
- Status last verified
- Sep 2020
- First submitted
- 2 Nov 2009
- Last updated
- 25 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Induction Therapy With Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation in Patients With AL Amyloidosis
- ClinicalTrials.gov ID
- NCT01083316
- Acronym / sponsor ID
- H-28441
- Conditions
- Amyloidosis
- Keywords
- Amyloid, Amyloidosis, AL Amyloidosis, Primary Amyloidosis, Stem Cell Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Boston Medical CenterUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Sep 2009 (actual)
- Primary completion
- Aug 2013 (actual)
- Study completion
- 4 Sep 2020 (actual)
- First posted
- 9 Mar 2010 (estimated)
- Results
- Posted 6 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The drugs dexamethasone and bortezomib are both FDA-approved for the treatment of multiple myeloma, a disease very similar to amyloidosis. However, they are currently investigational for the treatment of amyloidosis.
We want to find out if the addition of dexamethasone and bortezomib to standard high dose chemotherapy and stem cell transplant can help improve response.
Standard treatment includes four steps: 1) Stem Cell Mobilization (standard) 2) Stem Cell Collection (standard) 3) Conditioning Regimen (Melphalan chemotherapy). The conditioning regimen helps to kill the abnormal cells in the body and makes room in the bone marrow for new blood stem cells to grow. 4) Stem Cell Infusion
Participants in this study will have an additional treatment step called "induction therapy", designed as the first step towards reducing the number of abnormal cells in the body. Two cycles of the investigational drugs bortezomib and dexamethasone will be given during induction therapy. In addition, bortezomib will given as part of the conditioning regimen, in addition to the standard melphalan chemotherapy.
Detailed description
The drugs dexamethasone and bortezomib are both FDA-approved drugs for the treatment of multiple myeloma, a disease very similar to amyloidosis. However, they are currently investigational for the treatment of amyloidosis.
The investigators want to find out if the addition of dexamethasone and bortezomib to standard treatment of high dose chemotherapy and stem cell transplant can help improve response to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm - Investigational | Experimental | Drug: Bortezomib, Drug: Dexamethasone, Drug: MelphalanInduction: Bortezomib (Velcade) 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histological diagnosis of primary systemic (AL) amyloidosis based on:
- Note: Patients with senile, secondary, localized, dialysis-related or familial amyloidosis are not eligible. Confirmation of tissue diagnosis at all sites of organ dysfunction is encouraged, but not required.
- Must be at least 18 years of age.
- Must have a performance status of 0-2 by Southwest Oncology Group criteria
- Must have left ventricular ejection fraction (LVEF) at least 45% by echocardiogram within 60 days of enrollment
Key exclusion criteria (11 listed)
- No overt multiple myeloma (over 30% bone marrow plasmacytosis, extensive (great than 2) lytic lesions, hypercalcemia).
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 3 years.
- No known to be HIV positive.
- No platelet count of less than or equal to 70,000 within 14 days before enrollment.
- No absolute neutrophil count of less than or equal to 1000 within 14 days before enrollment.
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 |
|---|---|---|
| BortezomibAlso: VelcadeInduction: Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 | Drug | Single Arm - Investigational |
| DexamethasoneAlso: DecadronInduction: Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days | Drug | Single Arm - Investigational |
| MelphalanAlso: AlkeranConditioning: Melphalan 70-100 mg/m2/day IV on days -2 and -1 | Drug | Single Arm - Investigational |
Primary outcome
Number of Participants With Disease Response
Time frame: One year
Complete response: Normal serum free light chain ratio and Negative serum and urine immunofixation electrophoresis Very good partial response: Difference in serum free light chains less than 40 mg/L Partial Response: >50% Reduction in the difference in serum free light chains
Number of Participants Surviving at 100 Days Post Transplant
Time frame: 100 days
Number of Participants Proceeding to Transplant Following Induction
Time frame: 2 months
1 secondary outcome
Number of Participants Surviving at 5 Years
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Boston Medical Center Active Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Amyloidosis
Not yet recruiting
Acupressure as Long-term Intervention to Slow the Progression of Early/Mild Alzheimer's Disease
Alzheimer's Disease
Active, not recruitingPhase 2
A Study to Evaluate the Safety and Biomarker Effects of RO7269162 in Participants at Risk for or at the Prodromal Stage of Alzheimer's Disease (AD)
Alzheimer's Disease
Active, not recruitingObservational study
A Retrospective Observational Study of Epidemiology and Outcomes in Transthyretin Amyloid Cardiomyopathy in Germany
ATTR-CM (Transthyretin Amyloid Cardiomyopathy)
Active, not recruitingPhase 3
EPIC-ATTR: A Study to Evaluate the Effect of Eplontersen on the Transthyretin Reduction and Long-term Safety in Chinese Subjects With Transthyretin Amyloid Cardiomyopathy
Transthyretin Amyloid Cardiomyopathy
RecruitingObservational study
PET Imaging in the Baltimore Longitudinal Study of Aging (BLSA)
Aging
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.
Vaishali Sanchorawala, MD principal investigator
Boston Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bortezomib, Dexamethasone and Melphalan in people with Amyloidosis, run by Boston Medical Center at 1 site 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 13 inclusion and 11 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 25 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 6 Feb 2017). 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?
Number of Participants With Disease Response (time frame: One year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 25 Sep 2020.