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AmyloidosisPhase 1/2NCT00621400

Lenalidomide in Combination With Melphalan and Dexamethasone in Newly-diagnosed Light-chain (AL)-Amyloidosis

A Phase 1/2 study testing Lenalidomide, Melphalan and Dexamethasone in people with Amyloidosis, run by Nantes University Hospital at 12 sites in France.

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

Amyloidosis results from tissue deposition of amyloid protein, composed mainly by the fragments of monoclonal immunoglobulin heavy chains or light chains. Accumulation of amyloid protein progressively disrupts normal tissue structure and ultimately leads to organ failure, most frequently in the kidneys, heart, liver… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Amyloidosis
What is being tested?
Lenalidomide, Melphalan and Dexamethasone
Type of treatment
Pill or oral medicine
How many people
27 participants
Where
12 sitesFrance
Study dates
Jan 2008to Dec 2009
Phase
Phase 1/2
Are there results?
None posted in the registry

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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • De novo systemic biopsy proven AL-amyloidosis.
  • Measurable organ site involvement consistent with the diagnosis.
  • Adequate organ function defined as
  • Absolute neutrophil count > 1.0 x 109/L;
  • platelet count > 100x109/L;
  • AST (SGOT) and ALT (SGPT) < 2 x UNL;
Show all 17Show fewer
  • Total bilirubin £ 1.5 mg/dL ;
  • creatinin serum level <150µmol/L (1.5mg/dl);
  • Evaluable immunochemical abnormalities, including abnormal serum free light chain assay with an increase of either kappa or lambda light chain level.
  • ECOG performance status of £ 2 at study entry (see Appendix BB).
  • Age between18 and 70 years at the time of signing the informed consent form.
  • Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL at screening visit and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
  • Able to understand and voluntarily sign an informed consent form.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Able to take antithrombotic medicines such as low molecular weight heparin or warfarin (if needed).
  • Disease free of prior malignancies for > 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
  • Subjects affiliated with an appropriate social security system.

Who cannot join

  • Symptomatic multiple myeloma: multiple myeloma with related organ of tissue impairment (ROTI) according to the International Myeloma Working Group (16)
  • Any other uncontrolled medical condition or comorbidity that might interfere with subject's participation.
  • Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
  • Use of any other experimental drug or therapy within 28 days of baseline.
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
  • Any prior treatment for amyloidosis.
  • Known positive for HIV or infectious hepatitis, type A, B or C.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

France12 sites

  • CHRU d'Amiens

    Amiens, 80054

  • CHRU de Lille

    Lille, 59037

  • CHU de Limoges

    Limoges, 87042

  • CHU de Nantes

    Nantes, 44093

  • Hôpital Saint-Louis

    Paris, 75475

  • Hôpital Pitié Salpetrière

    Paris, 75651

  • Hôpital necker

    Paris, 75743

  • Hôpitaux Civils de Lyon

    Pierre-Bénite, 69495

  • CHU de Poitiers

    Poitiers, 86021

  • CHU de Rennes

    Rennes, 35203

  • CHU de Toulouse

    Toulouse, 31059

  • CHRU deTours

    Tours, 37044

Other trials in France

About this study

Official title: A Multicenter Phase I/II Dose Escalation Study of Lenalidomide in Combination With Melphalan and Dexamethasone in Subjects With Newly-diagnosed Light-chain (AL)-Amyloidosis

Amyloidosis results from tissue deposition of amyloid protein, composed mainly by the fragments of monoclonal immunoglobulin heavy chains or light chains. Accumulation of amyloid protein progressively disrupts normal tissue structure and ultimately leads to organ failure, most frequently in the kidneys, heart, liver and peripheral nervous system. A recently completed French prospective randomized trial, in patients presenting with newly AL-amyloidosis, compared two treatment regimens at the time of diagnosis: Melphalan-dexamethasone (conventional oral treatment), versus high dose of Melphalan followed by autologous stem cell transplantation (ASCT) (1). High-dose therapy was not associated with a better outcome. Melphalan-dex given monthly can be considered as the current standard of care, with a median survival of 56 months. The use of a combination of lenalidomide and dexamethasone has already been tested in patients with AL-amyloidosis (2). The initial dose of lenalidomide at 25 mg/day was poorly tolerated. However, a 15 mg/day dose regimen was well tolerated and effective, with an overall hematologic response rate of 67%. Hematologic responses were associated with clinical responses. Dispenzieri et al confirmed that the combination of Lenalidomide + dexamethasone achieved a 75% hematologic response rate, with a 42% organ response, and a median follow-up of 17 months in patients still receiving treatment (2006). These authors also recommended a lower dose of 15mg/day. The rationale for the present investigation is that addition of lenalidomide to the current standard of care (Melphalan-dexamethasone) might improve the hematologic response rate and the organ response rates both associated with a prolonged survival in patients with AL-amyloidosis. As the toxicity of the combination of M-dex + lenalidomide is unknown in patients with AL-amyloidosis, the dose of lenalidomide will start from the lowest one available, i.e., 5 mg/day and increased from 5 to 5 mg up to a maximum dose of 15 mg in combination with M-dex in 3 consecutive cohorts of patients, according to toxicity. When the optimal dose of lenalidomide will be defined, 9 additional patients will be included in the trial at the recommended dose-level to assess the feasibility of the combination M-dex-lenalidomide.

Conditions
Amyloidosis
Keywords
newly-diagnosed light-chain (AL)-amyloidosis
Medical subject headings
Amyloidosis, Immunoglobulin Light-chain Amyloidosis

What participants receive

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

  • LenalidomideDrug

    Also called Revlimid

    5 mg/day, orally for 21 days with 7 days rest (28 day cycle) for the first cohort; or 10mg/day, orally for 21 days with 7 days rest (28 day cycle) for the second cohort, 15mg/day, orally for 21 days with 7 days rest (28 day cycle) for the third cohort or 20mg/day, orally for 21 days with 7 days rest (28 day cycle) for the last and fourth cohort

  • MelphalanDrug

    Also called Alkeran

    0,18mg/Kg/day from day 1- 4

  • DexamethasoneDrug

    40mg/day from day 1- 4.

What is being measured

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

  1. Determination of MTD by evaluation of hematological and non hematological toxicity

    The primary endpoint is to evaluate the incidence of dose limiting toxicities (DLT) during the first cycle of lenalidomide at a given dose level in order to determine the maximal tolerated dose (MTD) in a dose escalating study design.

Secondary outcomes (6)

  1. Complete (CR) or partial (PR) response, according to criteria defined during the 10th International Symposium on Amyloidosis

    To determine the hematologic response

  2. disease progression from the date of the first dose to the date of the first observation of organ disease progression and observation of response

    To determine the rate of organ response

  3. Value of frequent measurements of free light chain assays

    To determine interest of frequent measurments of free light chain assays for patients

  4. Incidence of Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and laboratory abnormalities

    To assess the safety profile of the combination therapy

  5. time between first documentation of hematologic response and disease progression

    To measure hematological duration

  6. disease progression from the date of the first dose to the date of the first observation of hematologic disease progression

    Time to hematologic disease progression

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 2008 (estimated)
  2. Study startJan 2008
  3. Primary completionDec 2009
  4. Study completionDec 2009

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00621400
Sponsor's protocol ID
BRD 07/7-G
Other IDs
EudraCT 2007-004739-43
Status last verified
May 2010
First submitted
12 Feb 2008
Last updated
10 May 2011
Results posted
No
Data monitoring committee
No

Publications

  • Moreau P, Jaccard A, Benboubker L, Royer B, Leleu X, Bridoux F, Salles G, Leblond V, Roussel M, Alakl M, Hermine O, Planche L, Harousseau JL, Fermand JP. Lenalidomide in combination with melphalan and dexamethasone in patients with newly diagnosed AL amyloidosis: a multicenter phase 1/2 dose-escalation study. Blood. 2010 Dec 2;116(23):4777-82. doi: 10.1182/blood-2010-07-294405. Epub 2010 Aug 19.

    PubMed 20724537

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lenalidomide, Melphalan and Dexamethasone in people with Amyloidosis, run by Nantes University Hospital at 12 sites in France.

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 17 inclusion and 7 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 10 May 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in France. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Determination of MTD by evaluation of hematological and non hematological toxicity. 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 NCT00621400, 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 10 May 2011.

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