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Multiple MyelomaPhase 1/2MPTDNCT00406978

Melphalan, Prednisone, Thalidomide and Defibrotide in Relapsed Multiple Myeloma Patients

A Phase 1/2 study testing Prednisone, Melphalan and Thalidomide in people with Multiple Myeloma, run by Silvio Aime at 5 sites in Italy.

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

This study will evaluate the safety and the efficacy of the association of Melphalan/ Prednisone/Thalidomide/Defibrotide (MPTD) as salvage treatment in advanced and refractory myeloma patients. This association might further increase the response rate achieved by oral MPT regimen Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Prednisone, Melphalan and Thalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
5 sitesItaly
Study dates
Feb 2006to Apr 2014
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Each patient must meet all of the following inclusion criteria to be enrolled in the study:
  • Patient is of a legally consenting age as defined by local regulations.
  • Patient is, in the investigator(s) opinion willing and able to comply with the protocol requirements.
  • Patient has given 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
  • Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
  • Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study.
Show all 20Show fewer
  • Patient was previously diagnosed with multiple myeloma based on standard criteria (see Section 13.2).
  • Patient is relapsed after one line of treatment but less than three lines, including high-dose chemotherapy with stem cell support, conventional poli-chemotherapy, thalidomide- and melphalan-based regimens
  • Patient with primary refractory disease will be considered not eligible
  • Patient has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable, urine light-chain excretion of >200 mg/24 hours.
  • Patient has a Karnofsky performance status ≥60%.
  • Patient has a life-expectancy >3 months.
  • Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1, before study drug administration):
  • Platelet count ≥90 x 109/L without transfusion support within 7 days before the test.
  • Absolute neutrophil count (ANC) ≥ 1.00 x 109/L without the use of growth factors
  • Corrected serum calcium ≤14 mg/dL (3.5 mmol/L).
  • Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal (ULN).
  • Alanine transaminase (AST): ≤ 2.5 x the ULN.
  • Total bilirubin: ≤ 1.5 x the ULN.
  • Calculated or measured creatinine clearance: ≥20 mL/minute

Who cannot join

  • Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Pregnant or beast feeding females.
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Use of any other concomitant standard/experimental anti-myeloma drug or therapy
  • Known positive for HIV or active infectious hepatitis, type B or C
  • Other concurrent anticoagulation treatment

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Italy5 sites

  • Dip. Scienze Mediche & IRCAD-Università, UDA Ematologia

    Novara, Novara, 28100

  • Policlinico Monteluce, Clinica Medica I

    Perugia, Perugia, 06123

  • Divisione Di Ematologia, Ospedali Riuniti

    Reggio Calabria, Reggio Calabria

  • Servizio di Ematologia, Azienda Ospedaliera S. Maria Nuova

    Reggio Emilia, Reggio Emilia, 42100

  • Div. Univ. Di Ematologia, Az. Osp. San Giovanni Battista

    Torino, TO, 10126

Other trials in Italy

About this study

Official title: A Phase I/II, Multi-Center, Open Label Study of Melphalan, Prednisone, Thalidomide and Defibrotide in Advanced and Refractory Multiple Myeloma Patients

This study will evaluate the safety and the efficacy of the association of Melphalan/ Prednisone/Thalidomide/Defibrotide (MPTD) as salvage treatment in advanced and refractory myeloma patients. This association might further increase the response rate achieved by oral MPT regimen

Read the detailed description

Defibrotide (DF) is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects, which has been shown to be active in various microangiopathies, including the treatment and prophylaxis of veno-occlusive disease. While DF has minimal inhibitory effect on multiple myeloma (MM) in cell isolates, it showed single agent activity on human MM xenografts in SCID/NOD mice and markedly increased responsiveness of MM to cytotoxic agents, including melphalan, cyclophosphamide and dexamethasone in the same models. DF might thus enhance the response rate of Melphalan, Prednisone and Thalidomide, while protecting against the prothrombotic state seen with this combination in the treatment of MM. In this multicenter, open label, non-randomised phase I/II trial, dosing safety and efficacy of melphalan, prednisone, thalidomide, and DF (MPTD) were determined in pts with relapsed/refractory MM.

Primary refractory or pts receiving therapeutic anticoagulation were excluded. Oral melphalan was administered at 0,25 mg/Kg on D1-4, oral prednisone at 1,5 mg/kg on D 1-4, thalidomide was delivered at 50 mg on D1-35 on cycle 1 and at 100 mg from cycle 2 to cycle 6.

Level + 1 DF = 17 mg/Kg i.v. or 2.4 g p.o. D1-4, followed by 1.6 g p.o. through D 35 Level + 2 DF = 34 mg/Kg i.v. or 4.8 g p.o. D 1-4, followed by 3.2 g p.o. through D 35 Level + 3 DF = 51 mg/Kg i.v. or 7.2 g p.o. D 1-4, followed by 4.8 g p.o. through D 35.

Each course was repeated every 35d for a total of 6 courses and no DVT prophylaxis was used.

Being tested
Prednisone, Melphalan, Thalidomide, Defibrotide
Keywords
MYELOMA, THALIDOMIDE, DEFIBRODITE
Medical subject headings
Multiple Myeloma, Neoplasms, Plasma Cell

What participants receive

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

  • PrednisoneDrug

    Prednisone will be given orally at the dose of 1.5 mg/Kg for 4 days followed by a 31-day rest period (days 5 through 35)

  • MelphalanDrug

    Melphalan will be given orally at the dose of 0.25 mg/Kg for 4 days,

  • ThalidomideDrug

    Thalidomide will be administered orally at the initial dose of 50 mg/day p.o. once daily, with increment of 50 mg after a month to acceptable tolerance (maximum 100 mg), continuously for the entire 6 courses.

  • DefibrotideDrug

    Lev - 1 Def = 10 mg/Kg (max 0.6 g) on days 1-4, followed by 1.2 g (400 mg every 8 hours) p.o. through day 35 Lev - 1 Def = 1.2 g p.o (400 mg every 8 hours) on days 1-4, followed by 1.2 g (400 mg every 8 hours) p.o. through day 35 Level + 1 Def = 17 mg/Kg (max 1.2 g) on days 1-4, followed by 1.6 g p.o. (400 mg every 6 hours) through day 35 Lev + 1 Def = 2.4 g p.o. (400 mg every 4 hours) on days 1-4, followed by 1.6 g p.o. (400 mg every 6 hours) through day 35 Lev + 2 Def = 34 mg/Kg (max 2.4 g) as a i.v. injection on days 1-4, followed by 3.2 g p.o. (800 mg every 6 hours) through day 35 Lev + 2 Def = 4.8 g p.o. (800 mg every 4 hours) on days 1-4, followed by 3.2 g p.o. (800 mg every 6 hours) through day 35 Lev + 3 Def = 51mg/Kg (max 3.6 g) as a i.v. injection on days 1-4, followed by 4.8 g p.o. (1200 mg every 6 hours) through day 35 Lev + 3 Def = 7.2 g p.o.(1200 mg every 4 hours ) on days 1-4, followed by 4.8 g p.o. (1200 mg every 6 hours) given p.o. through day 35

Study groups in NCT00406978
Study groupRoleWhat they receive
MPTDExperimentalNot described
Receives: Drug: Prednisone; Drug: Melphalan; Drug: Thalidomide; Drug: Defibrotide

What is being measured

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

  1. The safety will be assessed by showing DLT and maximum tolerated dose (MTD) of defibrotide when administered in combination with MPT

    The DLT is defined by the development of febrile neutropenia, or Grade 4 neutropenia >= a week, or Grade 4 hematologic toxicity except neutropenia, or any >= Grade 3 non-hematologic toxicity considered by investigators to be related to study drug(s) in >30% of pts.

    MTD: maximum tolerated dose

    Measured: 7 months

  2. The efficacy will be assessed by showing at least 55% of patients in a minimal response (MR) or at least 10 % of pts in near complete remission (nCR).

    Measured: 7 months

Secondary outcomes (3)

  1. prolongation of progression-free survival

    Measured: it will be evaluated from the date of enrolling until the date of first documented evidence of the end point.

  2. duration of progression-free survival

    Measured: it will be evaluated from the date of enrolling until the date of first documented evidence of the end point.

  3. prolongs overall survival

    Measured: it will be evaluated from the date of enrolling until the date of first documented evidence of the end point.

Timeline

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

  1. First posted4 Dec 2006 (estimated)
  2. Study startFeb 2006
  3. Primary completionSep 2010
  4. Study completionApr 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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00406978
Sponsor's protocol ID
MM2005
Acronym
MPTD
Status last verified
May 2016
First submitted
30 Nov 2006
Last updated
10 May 2016
Results posted
No
Data monitoring committee
No

Publications

  • Buzaid AC, Durie BG. Management of refractory myeloma: a review. J Clin Oncol. 1988 May;6(5):889-905. doi: 10.1200/JCO.1988.6.5.889.

    PubMed 2452861

  • Palumbo A, Bertola A, Falco P, Rosato R, Cavallo F, Giaccone L, Bringhen S, Musto P, Pregno P, Caravita T, Ciccone G, Boccadoro M. Efficacy of low-dose thalidomide and dexamethasone as first salvage regimen in multiple myeloma. Hematol J. 2004;5(4):318-24. doi: 10.1038/sj.thj.6200403.

    PubMed 15297848

  • Blade J, Samson D, Reece D, Apperley J, Bjorkstrand B, Gahrton G, Gertz M, Giralt S, Jagannath S, Vesole D. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol. 1998 Sep;102(5):1115-23. doi: 10.1046/j.1365-2141.1998.00930.x. No abstract available.

    PubMed 9753033

  • McKean-Cowdin R, Feigelson HS, Ross RK, Pike MC, Henderson BE. Declining cancer rates in the 1990s. J Clin Oncol. 2000 Jun;18(11):2258-68. doi: 10.1200/JCO.2000.18.11.2258.

    PubMed 10829046

  • Alexanian R, Barlogie B, Tucker S. VAD-based regimens as primary treatment for multiple myeloma. Am J Hematol. 1990 Feb;33(2):86-9. doi: 10.1002/ajh.2830330203.

    PubMed 2301376

  • Palumbo A, Larocca A, Genuardi M, Kotwica K, Gay F, Rossi D, Benevolo G, Magarotto V, Cavallo F, Bringhen S, Rus C, Masini L, Iacobelli M, Gaidano G, Mitsiades C, Anderson K, Boccadoro M, Richardson P; Italian Multiple Myeloma Network GIMEMA. Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial. Haematologica. 2010 Jul;95(7):1144-9. doi: 10.3324/haematol.2009.017913. Epub 2010 Jan 6.

    PubMed 20053869

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Prednisone, Melphalan and Thalidomide in people with Multiple Myeloma, run by Silvio Aime at 5 sites in Italy.

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 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 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Italy. 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?

The safety will be assessed by showing DLT and maximum tolerated dose (MTD) of defibrotide when administered in combination with MPT (time frame: 7 months). The study lists 2 primary outcomes in all. 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 NCT00406978, which also lists 6 linked publications.

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 2016.

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