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Multiple Myeloma and Plasma Cell NeoplasmPhase 3NCT00477971

Low-Dose Melphalan and Dexamethasone Compared With High-Dose Melphalan Followed By Autologous Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis

A Phase 3 study testing filgrastim, dexamethasone and melphalan in people with Multiple Myeloma and Plasma Cell Neoplasm, 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
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Trial summary

RATIONALE: Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of plasma 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
What is being tested?
filgrastim, dexamethasone and melphalan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
89 participants
Where
1 siteUnited States
Study dates
Oct 2005to Dec 2014
Phase
Phase 3
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

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary systemic amyloidosis
  • Amyloid light-chain (AL) disease
  • Monoclonal protein by immunoelectrophoresis or immunofixation of the serum or urine OR abnormal free light-chain ratio
  • The following amyloid syndromes* are allowed:
  • Amyloid hepatomegaly
  • Cardiomyopathy
  • Proteinuria
  • Peripheral or autonomic neuropathy
  • Soft tissue involvement including the tongue, submandibular tissues, and vascular claudication
  • Diffuse interstitial pulmonary AL disease allowed if pulmonary function is adequate to allow safe transplantation NOTE: *Presence of amyloid deposits in a plasmacytoma or in bone marrow vessels in an asymptomatic patient does not constitute an amyloid syndrome
  • No secondary or familial amyloidosis
  • No multiple myeloma with lytic or destructive bone lesions or myeloma cast nephropathy
  • No multiple myeloma with > 30% plasma cells in the bone marrow
  • No amyloidosis manifested only by carpal tunnel syndrome or purpura

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Platelet count ≥ 100,000/mm³
  • Bilirubin ≤ 2.0 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 6 times ULN
  • Creatinine ≤ 3.0 mg/dL
  • No NYHA class IV heart disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • No HIV positivity

PRIOR CONCURRENT THERAPY:

  • Prior alkylating agents, immunosuppressive drugs, or steroids allowed provided they were given for < 1 month
  • Therapeutic steroid doses of ≤ 15 mg per day (or equivalent) allowed at discretion of physician
  • No concurrent participation in another clinical trial involving a pharmacologic agent

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 III Trial of Stem Cell Transplantation Compared to Parenteral Melphalan and Oral Dexamethasone in the Treatment of Primary Systemic Amyloidosis (AL)

RATIONALE: Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having an autologous stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher doses of chemotherapy to be given so that more plasma cells are killed. By reducing the number of plasma cells, the disease may progress more slowly. It is not yet known whether combination chemotherapy is more effective than chemotherapy followed by an autologous stem cell transplant in treating primary systemic amyloidosis.

PURPOSE: This randomized phase III trial is studying the side effects and how well giving low-dose melphalan together with dexamethasone works compared with high-dose melphalan followed by an autologous stem cell transplant in treating patients with primary systemic amyloidosis.

Read the detailed description

OBJECTIVES:

Primary

  • Compare hematologic response rate in patients with primary systemic amyloidosis treated with conventional chemotherapy comprising low-dose melphalan and dexamethasone vs high-dose melphalan followed by autologous stem cell transplantation.
  • Compare the toxicity of these regimens in these patients.

Secondary

  • Compare the overall and progression-free survival of patients treated with these regimens.
  • Compare the regression of organ involvement in patients treated with these regimens.
  • Compare the duration of response in patients treated with these regimens.
  • Correlate clonal burden and time to in vitro amyloid formation with clinical outcomes in patients treated with these regimens.
  • Compare quality of life of patients treated with these regimens.
  • Compare the information-seeking behavior in patients treated with these regimens.

OUTLINE: This is a comprehensive cohort study comprising a randomized option and a nonrandomized option. Patients consenting to randomization are stratified by risk group (high vs low) and ECOG performance status (0-1 vs 2). They are then randomized to 1 of 2 treatment arms. Patients not consenting to randomization choose their treatment arm.

  • Arm I: Patients receive low-dose melphalan IV over 15-30 minutes on day 1 or orally once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan IV over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.

Blood and bone marrow samples are collected at baseline. Samples are examined by PCR, cDNA, and nucleotide sequence analysis to determine VH and VL gene families and carrier status. Urine is collected at baseline and analyzed for light-chain protein levels by exclusion chromatography.

Quality of life is assessed at baseline, at months 3, 9, and 12, at completion of study treatment, and then every 6 months for up to 5 years.

After completion of study treatment, patients are followed every 6 months for up to 10 years.

Being tested
filgrastim, dexamethasone, melphalan, autologous hematopoietic stem cell transplantation
Keywords
primary systemic amyloidosis
Medical subject headings
Multiple Myeloma, Neoplasms, Plasma Cell, Immunoglobulin Light-chain Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • filgrastimBiological

    No administration information given

  • dexamethasoneDrug

    Given orally

  • melphalanDrug

    Given IV or orally

  • autologous hematopoietic stem cell transplantationProcedure or surgery

    Given on day 0

Study groups in NCT00477971
Study groupRoleWhat they receive
Arm AActive comparatorPatients receive low-dose melphalan IV over 15-30 minutes on day 1 or orally once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses. Study treatment beyond one year is not allowed.
Receives: Drug: dexamethasone; Drug: melphalan
Arm BExperimentalPatients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan IV over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.
Receives: Biological: filgrastim; Drug: melphalan; Procedure: autologous hematopoietic stem cell transplantation

What is being measured

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

  1. Hematologic Response Rate

    Response that was confirmed on 2 consecutive evaluations during treatment. A hematologic response consisted of a Complete response, Very Good Partial Response or Partial Response.

    • 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: 10 years

Secondary outcomes (2)

  1. 3 Year Overall Survival

    Percentage of patients who were alive at 3 years. The 3-year survival rate was estimated using the Kaplan Meier method.

    Measured: 3 years

  2. Organ Response to Treatment

    Organ response was evaluated on the basis of improvement of one or more affected organ; only one parameter was required to satisfy the criteria. Response needed to be maintained for a minimum of 3 months to be considered valid.

    Renal response required a 50% reduction in 24-hour urine protein excretion (at least 0.5 g/d) with stable creatinine. Cardiac response required one of >= 2-mm reduction in the interventricular septal (IVS) thickness by echocardiogram, or improvement of ejection fraction by >= 20%, or improvement by 2 NYHA classes without an increase in diuretic use. Hepatic response required either >= 50% decrease in (or normalization of) an initially elevated alkaline phosphatase level or reduction in the size of the liver by at least 2 cm by radiographic determination. Gastrointestinal tract improvement was defined as normalization of a low serum carotene level, or reduction of diarrhea to < 50% of previous movements/day, or decrease in fecal fat excretion by 50%.

    Measured: 10 years

Timeline

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

  1. First posted24 May 2007 (estimated)
  2. Study startOct 2005
  3. Primary completionJul 2012
  4. Study completionDec 2014

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 3
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00477971
Sponsor's protocol ID
CDR0000546745
Other IDs
P30CA015083, MC0482, 1691-05, NCI-2009-01329
Status last verified
Jun 2015
First submitted
23 May 2007
Last updated
17 May 2016
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing filgrastim, dexamethasone and melphalan in people with Multiple Myeloma and Plasma Cell Neoplasm, 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?

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 17 May 2016. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 21 Jul 2015). 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?

Hematologic Response Rate (time frame: 10 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 NCT00477971.

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 17 May 2016.

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