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Multiple MyelomaPhase 3NCT01134484

VELCADE-Thalidomide-Dexamethasone (VTD) vs Thalidomide-Dexamethasone (TD) Incorporated Into Double Autotransplantation for Untreated Multiple Myeloma (MM)

A Phase 3 study testing Velcade, Thalidomide and Dexamethasone in people with Multiple Myeloma, run by Michele Cavo at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Thalidomide-Dexamethasone (TD) is a standard induction therapy for Multiple Myeloma (MM). The present study is designed to compare TD with VELCADE-Thalidomide-Dexamethasone (VTD) as induction therapy in preparation for, and as consolidation after, melphalan-based double autologous stem cell transplantation for… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Multiple Myeloma
What is being tested?
Velcade, Thalidomide and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
480 participants
Where
1 siteItaly
Study dates
May 2006to Dec 2015
Phase
Phase 3
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmed diagnosis of symptomatic MM based on standard criteria.
  • No prior or current systemic therapy for MM, including steroids.
  • At least 18 years and less than 65 years of age.
  • Presence of quantifiable M protein in serum (e.g. greater than 1 g/dL for IgG MM, greater than 0.5 g/dL of IgA or IgD MM) or urine (e.g. greater than 200 mg/day for BJ MM).
  • Karnofsky performance status (PS) at least 60%.
  • Willing and able to comply with the protocol requirements.
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  • Agreement from both male and female patients to follow the risk management program established for the prevention of pregnancy, including double methods for contraception and beta-HCG tests for women of childbearing potential and contraception for males.
  • Adequate organ function, including heart, liver, kidney (serum creatinine less than 2 mg/dL)
  • Platelet count at least 70 x 10/mcL and absolute neutrophil count at least 1 x 10/mcl

Who cannot join

  • Diagnosis of asymptomatic MM or of MGUS based on standard criteria.
  • Diagnosis of non-secretory MM.
  • Diagnosis of AL Amyloidosis.
  • Prior or current systemic therapy for MM, including steroids (with exception of bisphosphonates).
  • Patient has received other investigational drugs within 30 days before enrollment.
  • Female subjects pregnant or breastfeeding
Show all 18Show fewer
  • Patient has Grade 2 or higher peripheral neuropathy (NCI criteria).
  • Patient has a prior history of thrombosis or venous thromboembolism or pulmonary embolism.
  • Patient has a previous diagnosis of antiphospholipid antibodies or lupus anticoagulant, factor V Leiden mutation, prothrombin G21210A mutation, antithrombin, protein C or S deficiency.
  • Patient has a clear indication to receive a specific other anti-platelet therapy (e.g. clopidogrel, ticlopidine).
  • Patient has a clear indication to receive long-term anticoagulant therapy (e.g. prosthetic heart valve, atrial fibrillation).
  • Active bleeding or high risk of bleeding (gastrointestinal bleeding within the past 12 months; endoscopic diagnosis of peptic ulcer disease or ulcerative esophagitis within the past 6 months unless there is documented endoscopic evidence of healing; intracranial bleeding within the past year; amyloidosis; known bleeding diathesis).
  • Seropositive for HIV, or active hepatitis A, B or C infection.
  • Poorly controlled hypertension or diabetes mellitus (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before the start of therapy) or other serious medical or psychiatric conditions that could interfere with adherence to or completion of this study.
  • Patient has hypersensitivity to bortezomib, boron or mannitol.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Previous or concurrent malignancies at other sites, with the exception of appropriately treated localized epithelial skin or cervical cancer. Patients with remote histories (>5 years) of other cured tumors may be entered.
  • Receipt of extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 4 weeks before enrolment.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • AOU di Bologna Policlinico S.Orsola-Malpighi, UO di Ematologia

    Bologna, 40138

Other trials in Italy

About this study

Official title: A Phase 3, Prospective, Randomized Clinical Study of VELCADE-Thalidomide-Dexamethasone (VTD) Versus Thalidomide-Dexamethasone (TD) for Previously Untreated Multiple Myeloma (MM) Patients Who Are Candidates to Receive Double Autologous Transplantation

Thalidomide-Dexamethasone (TD) is a standard induction therapy for Multiple Myeloma (MM). The present study is designed to compare TD with VELCADE-Thalidomide-Dexamethasone (VTD) as induction therapy in preparation for, and as consolidation after, melphalan-based double autologous stem cell transplantation for previously untreated patients aged ≤65 years with symptomatic MM. Primary study endpoint is the rate of complete response (CR) plus near-complete response (nCR) to induction treatment. Secondary endpoints include the rate of CR plus nCR to double transplantation and subsequent consolidation therapy, time to progression (TTP), progression-free survival (PFS),overall survival (OS) and toxicity profile of both VTD and TD.

Read the detailed description

This prospective phase 3 trial is aimed at evaluating whether, in comparison with standard TD, addition of Velcade to TD increases rate of CR and nCR from 15% to 30%, respectively. For this purpose, symptomatic patients aged 18-65 years with previously untreated MM and quantifiable M-protein in serum or urine are randomized (1:1) to receive induction therapy comprising three 3-week cycles of Velcade 1.3 mg/sqm, days 1, 4, 8, 11, thalidomide 100 mg, days 1-14, cycle 1, then 200 mg daily, and dexamethasone 40 mg, days 1, 2, 4, 5, 8, 9, 11, 12, or thalidomide and dexamethasone (same schedule and dosage as in VTD). Randomization to VTD or TD is stratified according to International Staging System disease stage at diagnosis. Following induction therapy, patients in both arms receive cyclophosphamide (4 g/sqm, day 0 and granulocyte colony-stimulating factor, 10 μcg/kg/day, from day +2) to collect autologous peripheral blood stem cells (minimum threshold CD34+ cells: 4 x 10^6/kg) and two subsequent courses of stem cell-supported high dose melphalan (200 mg/sqm), 3 to 6 months apart. Upon neutrophil (≥1 x 10^9/L) and platelet (≥75 x 10^9/L) recovery following the first autotransplantation, patients receive thalidomide (100 mg daily) and dexamethasone (40 mg, days 1-4 every 4 weeks) as bridge therapy until the day before the second transplantation.

Patients initially randomized to receive VTD or TD induction therapy are planned to receive two 5-week cycles of VTD (Velcade 1.3 mg/sqm, days 1, 8, 15, 22; thalidomide 100 mg daily; dexamethasone 40 mg, days 1, 2, 8, 9, 15, 16, 22, 23) or TD (thalidomide 100 mg daily; dexamethasone 40 mg, days 1-4 and 20-23) as consolidation therapy, starting 3 months after last transplant. Maintenance therapy comprise dexamethasone 40 mg, days 1-4, repeated monthly until relapse or progression.

Being tested
Velcade, Thalidomide, Dexamethasone, Peripheral Blood Stem Cell (PBSC) collection, First Autologous Transplantation
Keywords
autologous stem cell transplantation, complete remission, bortezomib, thalidomide, progression free survival, induction and consolidation therapy
Medical subject headings
Multiple Myeloma, Pathologic Complete Response

What participants receive

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

  • VelcadeDrug

    Also called Bortezomib

    • INDUCTION THERAPY: 1.3 mg/sqm as a bolus i.v. injection on days 1, 4, 8 and 11 (3 courses, 21 days each)
    • REMISSION CONSOLIDATION THERAPY: 1.3 mg/sqm as a bolus i.v. injection on days 1, 8, 15 and 22 (2 courses, 35 days each)

  • ThalidomideDrug

    Also called Talidomide

    • INDUCTION THERAPY: 100 mg/d on days 1-14, 200 mg/d on days 15-63 (in case of delay of HD-CTX , Thalidomide will be continued until the day before Cyclophosphamide as priming therapy for PBSC collection)
    • AFTER PBSC COLLECTION: 100 mg/d from day after last PBSC collection until the day before first course of MEL-200
    • AFTER FIRST TRANSPLANTATION: 100 mg/d from recovery of hematopoiesis until the day before the second course of MEL-200
    • REMISSION CONSOLIDATION THERAPY (starting 3 months after the second autologous transplantation): 100 mg/d days 1-70

  • DexamethasoneDrug

    Also called Soldesam

    • INDUCTION THERAPY
    1. VTD ARM: 40 mg/d days 1-2, 4-5, 8-9 and 11-12 (3 cycles, 21 days each)
    2. TD ARM: 40 mg/d days 1-4 and 9-12 (3 cycles, 21 days each)
    • AFTER PBSC COLLECTION: 40 mg/d for 4 days (starting the same day of resumption of Thalidomide)
    • AFTER FIRST TRANSPLANTATION: 40 mg/d for 4 days (starting the same day of resumption of Thalidomide) and repeated every 28 days, for 3 months
    • REMISSION CONSOLIDATION THERAPY (starting 3 months after the second autologous transplantation)
    1. VTD ARM: 40 mg/d days 1-2, 8-9, 15-16 and 22-23 (2 cycles, 35 days each)
    2. TD ARM: 40 mg/d days 14 and 20-23 (2 cycles, 35 days each)

  • Peripheral Blood Stem Cell (PBSC) collectionProcedure or surgery

    • Cyclophosphamide (CTX): 4 g/sqm given in a single day (day 0)
    • G-CSF: 10 µcg/kg/d, starting on day +2 from CTX and continuing until completion of PBSC collection

  • First Autologous TransplantationProcedure or surgery

    • HIGH-DOSE MELPHALAN (MEL-200): 200 mg/sqm, given as a single dose i.v. (day -2) followed by PBSC infusion 48 hours later (day 0)
    • G-CSF: 5 µcg/kg daily starting from day +6 after grafting and continuing until the patient's ANC is more than 0.5x10^9/L for 3 consecutive days

  • Second Autologous TransplantationProcedure or surgery

    • HIGH-DOSE MELPHALAN (MEL-200): 200 mg/sqm, given as a single dose i.v. (day -2) followed by PBSC infusion 48 hours later (day 0)
    • G-CSF: 5 µcg/kg daily starting from day +6 after grafting and continuing until the patient's ANC is more than 0.5x10^9/L for 3 consecutive days
Study groups in NCT01134484
Study groupRoleWhat they receive
VTDExperimentalNot described
Receives: Drug: Velcade; Drug: Thalidomide; Drug: Dexamethasone; Procedure: Peripheral Blood Stem Cell (PBSC) collection; Procedure: First Autologous Transplantation; Procedure: Second Autologous Transplantation
TDActive comparatorNot described
Receives: Drug: Thalidomide; Drug: Dexamethasone; Procedure: Peripheral Blood Stem Cell (PBSC) collection; Procedure: First Autologous Transplantation; Procedure: Second Autologous Transplantation

What is being measured

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

  1. Rate of CR+nCR to induction treatment

    Responses to induction therapy were reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the European Group for Blood and Marrow Transplantation (EBMT), with the addition of nCR (100% M-protein reduction by electrophoresis, but immunofixation-positive) and very good partial response (VGPR) (at least 90% serum and urine M-protein reduction) categories. Comparisons of response rates between treatment arms are performed using Fisher's exact test.

    Measured: 63 days after the start day of either TD or VTD as induction therapy

Secondary outcomes (5)

  1. Rate of CR+nCR to autotransplantation(s) and subsequent consolidation therapy

    Responses to autotransplantation(s) and consolidation therapy were reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the EBMT, with the addition of nCR and VGPR categories. Comparisons of response rates between treatment arms are performed using Fisher's exact test. Comparisons of response rates between treatment arms are performed using Fisher's exact test.

    Measured: 90 days after the second autologous transplantation and 70 days after the beginning of either TD or VTD as consolidation therapy

  2. Time To Progression (TTP)

    TTP is defined as time from start of induction treatment with either TD or VTD to relapse or progression, as evaluated according to EBMT criteria. Comparison of TTP between treatment arms is performed using the log-rank test; distributions are estimated using Kaplan-Meier methodology.

    Measured: Average time period between the start day of either TD or VTD as induction therapy and the day of relapse or progression

  3. Progression-Free Survival (PFS)

    PFS is defined as time from start of treatment to progression/relapse, or death, whichever occurs firstly. Comparison of PFS between treatment arms is performed using the log-rank test; distributions are estimated using Kaplan-Meier methodology.

    Measured: Average time period between the start day of either TD or VTD as induction therapy and the day of relapse or progression or death, whichever occurs firstly

  4. Overall Survival (OS)

    OS is defined as time from start of treatment to death. Comparison of OS between treatment arms is performed using the log-rank test; distributions are estimated using Kaplan-Meier methodology.

    Measured: Average time period between the start day of either TD or VTD as induction therapy and the day of death, due to any cause

  5. Safety

    Safety is monitored until 30 days after the last dose of study drug. Toxicities are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Rates of adverse events are compared between treatment arms using the chi-square test.

    Measured: Average time period between the start day of either TD or VTD as induction therapy and the day of any toxicity/adverse event(s) recorded during and after study drug administration

Timeline

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

  1. First posted2 Jun 2010 (estimated)
  2. Study startMay 2006
  3. Primary completionAug 2008
  4. Study completionDec 2015 (estimated)

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
480 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01134484
Sponsor's protocol ID
MM-BO2005
Other IDs
2005-003723-39, 26866138-MMY-3006, 2005
Status last verified
Jul 2012
First submitted
28 May 2010
Last updated
20 Jul 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • Tacchetti P, Pantani L, Patriarca F, Petrucci MT, Zamagni E, Dozza L, Galli M, Di Raimondo F, Crippa C, Boccadoro M, Barbato S, Tosi P, Narni F, Montefusco V, Testoni N, Spadano A, Terragna C, Pescosta N, Marzocchi G, Cellini C, Galieni P, Ronconi S, Gobbi M, Catalano L, Lazzaro A, De Sabbata G, Cangialosi C, Ciambelli F, Musto P, Elice F, Cavo M; GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto Italian Myeloma Network). Bortezomib, thalidomide, and dexamethasone followed by double autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GIMEMA-MMY-3006): long-term follow-up analysis of a randomised phase 3, open-label study. Lancet Haematol. 2020 Dec;7(12):e861-e873. doi: 10.1016/S2352-3026(20)30323-9.

    PubMed 33242443

  • Zamagni E, Nanni C, Dozza L, Carlier T, Bailly C, Tacchetti P, Versari A, Chauvie S, Gallamini A, Gamberi B, Caillot D, Patriarca F, Macro M, Boccadoro M, Garderet L, Barbato S, Fanti S, Perrot A, Gay F, Sonneveld P, Karlin L, Cavo M, Bodet-Milin C, Moreau P, Kraeber-Bodere F. Standardization of 18F-FDG-PET/CT According to Deauville Criteria for Metabolic Complete Response Definition in Newly Diagnosed Multiple Myeloma. J Clin Oncol. 2021 Jan 10;39(2):116-125. doi: 10.1200/JCO.20.00386. Epub 2020 Nov 5.

    PubMed 33151787

  • Jamet B, Morvan L, Nanni C, Michaud AV, Bailly C, Chauvie S, Moreau P, Touzeau C, Zamagni E, Bodet-Milin C, Kraeber-Bodere F, Mateus D, Carlier T. Random survival forest to predict transplant-eligible newly diagnosed multiple myeloma outcome including FDG-PET radiomics: a combined analysis of two independent prospective European trials. Eur J Nucl Med Mol Imaging. 2021 Apr;48(4):1005-1015. doi: 10.1007/s00259-020-05049-6. Epub 2020 Oct 2.

    PubMed 33006656

  • Pezzi A, Cavo M, Biggeri A, Zamagni E, Nanni O. Inverse probability weighting to estimate causal effect of a singular phase in a multiphase randomized clinical trial for multiple myeloma. BMC Med Res Methodol. 2016 Nov 9;16(1):150. doi: 10.1186/s12874-016-0253-9.

    PubMed 27829371

  • Sonneveld P, Goldschmidt H, Rosinol L, Blade J, Lahuerta JJ, Cavo M, Tacchetti P, Zamagni E, Attal M, Lokhorst HM, Desai A, Cakana A, Liu K, van de Velde H, Esseltine DL, Moreau P. Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol. 2013 Sep 10;31(26):3279-87. doi: 10.1200/JCO.2012.48.4626. Epub 2013 Jul 29.

    PubMed 23897961

  • Cavo M, Pantani L, Petrucci MT, Patriarca F, Zamagni E, Donnarumma D, Crippa C, Boccadoro M, Perrone G, Falcone A, Nozzoli C, Zambello R, Masini L, Furlan A, Brioli A, Derudas D, Ballanti S, Dessanti ML, De Stefano V, Carella AM, Marcatti M, Nozza A, Ferrara F, Callea V, Califano C, Pezzi A, Baraldi A, Grasso M, Musto P, Palumbo A; GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto) Italian Myeloma Network. Bortezomib-thalidomide-dexamethasone is superior to thalidomide-dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2012 Jul 5;120(1):9-19. doi: 10.1182/blood-2012-02-408898. Epub 2012 Apr 12.

    PubMed 22498745

  • Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, Di Raimondo F, Crippa C, Zamagni E, Palumbo A, Offidani M, Corradini P, Narni F, Spadano A, Pescosta N, Deliliers GL, Ledda A, Cellini C, Caravita T, Tosi P, Baccarani M; GIMEMA Italian Myeloma Network. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18;376(9758):2075-85. doi: 10.1016/S0140-6736(10)61424-9. Epub 2010 Dec 9.

    PubMed 21146205

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Velcade, Thalidomide and Dexamethasone in people with Multiple Myeloma, run by Michele Cavo at 1 site 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 9 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 20 Jul 2012. 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 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 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?

Results are not available in the source record.

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?

Rate of CR+nCR to induction treatment (time frame: 63 days after the start day of either TD or VTD as induction therapy). 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 NCT01134484, which also lists 7 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 20 Jul 2012.

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