AzTrials
AzTrials

Primary Systemic AmyloidosisPhase 2NCT01072773

Bortezomib, Cyclophosphamide, and Dexamethasone in Treating Patients With Primary Systemic Light Chain Amyloidosis

A Phase 2 study testing bortezomib, cyclophosphamide and dexamethasone in people with Primary Systemic Amyloidosis, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Primary Systemic Amyloidosis
What is being tested?
bortezomib, cyclophosphamide and dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
Mar 2010to Jun 2012
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

  • Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens
  • Measurable disease of amyloid light chain amyloidosis as defined by at least ONE of the following: serum monoclonal protein >= 1.0 g by protein electrophoresis, > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis, serum free light-chain >= 7.5 mg/dL with an abnormal kappa:lambda ratio
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2
  • Absolute neutrophil count >= 1000/uL
  • Platelet >= 75000/uL
  • Total bilirubin < 3.0 mg/dL
Show all 20Show fewer
  • Aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN)
  • Creatinine clearance >= 30ml/min
  • Women of childbearing potential should have a negative serum or urine pregnancy test done =< 7 days prior to registration, and should be 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
  • Previously treated amyloidosis; no limit to prior therapy provided there is adequate residual organ function
  • Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system or soft tissue); carpal tunnel syndrome skin purpura, or the presence of vascular amyloid on a bone marrow biopsy alone are not sufficient to meet criteria for "symptomatic organ involvement"
  • Renal involvement is defined as proteinuria (predominantly albumin) > 0.5 g/day in a 24- hour urine collection
  • Cardiac involvement is defined as the presence of a mean left ventricular wall thickness on echocardiogram greater than 12 mm in the absence of a history of hypertension or valvular heart disease, or in the presence of unexplained low voltage (< 0.5 mV) on the electrocardiogram
  • Hepatic involvement is defined as hepatomegaly (>= 2 cm below costal margin) on physical exam or an alkaline phosphatase > 1.5 x ULN
  • Peripheral nerve involvement is defined based on clinical history or abnormal sensory and/or motor findings on neurologic exam
  • Autonomic nerve involvement is defined as orthostasis, symptoms of nausea or dysgeusia, gastric atony by gastric emptying scan, diarrhea or constipation
  • Soft tissue and lymphatic involvement may be ascertained based on classic physical exam findings (macroglossia, shoulder pad sign, raccoon eyes, carpal tunnel syndrome, synovial enlargement, firm enlarged lymph nodes) or biopsy
  • 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 subject any time without prejudice to future medical care
  • Willingness to return to Mayo Clinic enrolling institution for follow-up

Who cannot join

  • Melphalan or other myelosuppressive agents =< 3 weeks prior to registration; non-myelosuppressive agents like thalidomide, or high dose corticosteroids <= 1week prior to registration
  • Concurrent use of corticosteroids, but patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than amyloid, i.e., adrenal insufficiency, rheumatoid arthritis, etc
  • Any of the following because this study involves an agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: pregnant women and nursing women
  • Other active malignancy =< 2 years prior to registration; EXCEPTIONS: Nonmelanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: If there is a history or prior malignancy, they must not be receiving any specific treatment for their cancer
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens including psychiatric illness/social situations that would limit compliance with study requirements
  • Known to be HIV positive
Show all 12Show fewer
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Clinically overt multiple myeloma (monoclonal Bone Marrow Plasma Count > 30%), and at least one of the following: bone lesions or hypercalcemia
  • History of myocardial infarction =< 6 months, or requiring use of ongoing maintenance drug therapy for life-threatening ventricular arrhythmias
  • Grade 3 sensory or grade 1 painful peripheral neuropathy
  • Known hypersensitivity to bortezomib, boron or mannitol
  • Cardiac syncope, uncompensated New York Heart Association (NYHA) Class 3 or 4 congestive heart failure or troponin T > 0.1 ng/mL

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase II Study of Bortezomib, Cyclophosphamide and Dexamethasone in Patients With Primary Systemic Light Chain Amyloidosis

RATIONALE: Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving bortezomib, cyclophosphamide, and dexamethasone together works in treating patients with primary systemic light chain amyloidosis.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the confirmed hematologic response rate of the combination of bortezomib, cyclophosphamide and dexamethasone in patients with primary systemic amyloidosis.

SECONDARY OBJECTIVES:

  1. Organ response rate of the bortezomib, cyclophosphamide and dexamethasone combination.

II. Severity and frequency of adverse events associated with bortezomib, cyclophosphamide and dexamethasone treatment in patients with primary systemic amyloidosis.

III. Time to progression.

IV. Survival.

OUTLINE: Patients receive bortezomib IV on days 1, 8, and 15 and oral cyclophosphamide and oral dexamethasone once daily on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 months for 2 years.

Medical subject headings
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 LDP 341, MLN341, PS-341, VELCADE

    1.3 mg/m^2, by IV on days 1, 8 and 15 every 28 days

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    300 mg/m^2, orally, on days 1, 8, 15 \& 22 every 28 days.

  • dexamethasoneDrug

    Also called Aeroseb-Dex, Decaderm, Decadron, Decaspray

    40 mg, orally, on days 1, 8, 15 \& 22 every 28 days

Study groups in NCT01072773
Study groupRoleWhat they receive
Bortez/Cyc/DexExperimentalBortezomib IV on days 1, 8, and 15, oral cyclophosphamide and oral dexamethasone once daily on days 1, 8, 15, and 22.
Receives: Drug: bortezomib; Drug: cyclophosphamide; Drug: dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With a Confirmed Hematologic Response

    Response that was confirmed on 2 consecutive evaluations during treatment.

    Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow.

    Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <=100 mg per 24 hours.

    Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200 mg per 24 hours; or >=50% decrease in difference between involved and uninvolved FLC levels.

    Measured: Duration of treatment (up to 12 cycles/months)

Secondary outcomes (5)

  1. Number of Participants With Treatment Related Adverse Events.

    Adverse events (AE) that are classified as either possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0). The maximum grade for each type of AE will be recorded for each patient. Grade refers to the severity of the AE.

    Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE, Grade 5: Death related AE

    Adverse events will be assessed using NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0.

    Measured: Duration on treatment (up to 12 cycles/months)

  2. Number of Participants With an Organ Response.

    The number of patients that acheived a response in an affected organ.

    Measured: Duration on treatment (up to 12 cycles/months)

  3. Overall Survival

    Survival time is defined as the time from registration to death due to any cause.

    Measured: Duration of Study (up to 5 years)

  4. Time to Disease Progression

    Time to disease progression is defined as the time from registration to the earliest date of documented disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had tumor progression at the time of their death

    Measured: Duration of Study (up to 5 years)

  5. Duration of Response

    Duration of response will be calculated from the date of first evidence of response until the date of progression in the subset of patients with confirmed hematologic responses.

    Measured: Duration of Study (up to 5 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2010 (estimated)
  2. Study startMar 2010
  3. Primary completionMar 2011
  4. Study completionJun 2012

Resources

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
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01072773
Sponsor's protocol ID
MC0985
Other IDs
NCI-2009-01564, 09-005736, MC0985, X05306
Status last verified
Mar 2014
First submitted
17 Feb 2010
Last updated
2 Apr 2014
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bortezomib, cyclophosphamide and dexamethasone in people with Primary Systemic Amyloidosis, run by Mayo Clinic 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 20 inclusion and 12 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 2 Apr 2014. 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 5 Dec 2012). 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 a Confirmed Hematologic Response (time frame: Duration of treatment (up to 12 cycles/months)). 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 NCT01072773.

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 2 Apr 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in