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Multiple MyelomaPhase 3NCT01093196

Lenalidomide and Dexamethasone Versus Melphalan Prednisone and Lenalidomide Versus Cyclophosphamide, Prednisone and Lenalidomide in Elderly Multiple Myeloma Patients

A Phase 3 study testing Melphalan, Prednisone, Lenalidomide, Cyclophosphamide, Prednisone, Lenalidomide and Lenalidomide, dexamethasone in people with Multiple Myeloma, run by Fondazione EMN Italy Onlus at 1 site in Italy.

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

This is a multicenter, randomized, controlled, 3 arm parallel group study designed to evaluate the efficacy and safety of three all-oral combinations: lenalidomide with dexamethasone (Rd) in comparison with lenalidomide in association with MP (MPR) and lenalidomide in association with cyclophosphamide - prednisone… 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?
Melphalan, Prednisone, Lenalidomide, Cyclophosphamide, Prednisone, Lenalidomide and Lenalidomide, dexamethasone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
660 participants
Where
1 siteItaly
Study dates
Oct 2009to 1 Jul 2024
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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performance of any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
  • Patient is 65 years old or older at the time of signing the informed consent or younger patients not candidate to high dose therapy
  • Female patient is either post-menopausal or surgically sterilized or, if at child-bearing potential†, must:
  • understand that the study medication could have an expected teratogenic risk
  • Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception*
Show all 38Show fewer
  • Implant**
  • Levonorgestrel-releasing intrauterine system (IUS)**
  • Medroxyprogesterone acetate depot
  • Tubal sterilisation
  • Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses
  • Ovulation inhibitory progesterone-only pills (i.e., desogestrel)
  • Combined oral contraceptive pills are not recommended. If a subject was using combined oral contraception, she must switch to one of the methods above. The increased risk of VTE continues for 4 to 6 weeks after stopping combined oral contraception.
  • prophylactic antibiotics should be considered at the time of insertion particularly in patients with neutropenia due to risk of infection
  • Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days before the start of study medication once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.
  • Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. These tests should be performed not more than 3 days before the start of next treatment. This requirement also applies to women of childbearing potential who practice complete and continued abstinence
  • Male subjects must
  • Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.
  • Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
  • All subjects must
  • Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
  • Agree not to share study medication with another person and to return all unused study drug to the investigator.
  • Patient was previously diagnosed with symptomatic MM based on standard criteria, and has measurable disease, defined as follows:
  • Secretory myeloma: 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;
  • Non-secretory myeloma: > 30% plasma cells in the bone marrow and at least one plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (i.e., MRI or CT scan).
  • Patient has a baseline bone marrow sample available for cytogenetics, that will be processed and eventually centralized within each country.
  • Patient has a Karnofsky performance status _ 60%.
  • Patient has a life-expectancy > 6 months
  • Patients must have a adequate cardiac function
  • Patients must have adequate pulmonary function
  • Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1):
  • Platelet count ≥ 75 x 109/L without transfusion support within 7 days before the test.
  • Absolute neutrophil count (ANC) ≥1.0 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 (ALT): ≤ 2.5 x the ULN.
  • Total bilirubin: ≤1.5 x the ULN.
  • Calculated or measured creatinine clearance: ≥30 mL/minute

Who cannot join

  • Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid; < to the equivalent of dexamethasone 40 mg/day for 4 days).
  • Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data from the study.
  • Pregnant or lactating females.
  • Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥3 years. Exceptions include the following: Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Division Of Hematology, A.O.U. Città della Salute e della Scienza di Torino

    Torino, TO, 10126

Other trials in Italy

About this study

Official title: A Phase 3, Intergroup Multicentre, Randomized, Controlled 3 Arm Parallel Group Study to Determine the Efficacy and Safety of Lenalidomide in Combination With Dexamethasone (RD) Versus Melphalan, Prednisone and Lenalidomide (MPR) Versus Cyclophosphamide, Prednisone and Lenalidomide (CPR) in Newly Diagnosed Elderly Multiple Myeloma Subjects

This is a multicenter, randomized, controlled, 3 arm parallel group study designed to evaluate the efficacy and safety of three all-oral combinations: lenalidomide with dexamethasone (Rd) in comparison with lenalidomide in association with MP (MPR) and lenalidomide in association with cyclophosphamide - prednisone (CPR) in newly diagnosed symptomatic MM patients. This protocol also provides a substudy designed to observe asymptomatic patients excluded to the protocol that in any case could be inserted in the study.

Read the detailed description

This is an intergroup multicenter, randomized, open label study designed to compare the efficacy and safety of Rd with MPR and CPR in newly diagnosed symptomatic MM patients who are 65 years of age or older. Potential study subjects will sign an informed consent prior to undergoing any study related procedure.

This study consists of 3 phases for each study subject: Pre-treatment, Treatment and Follow up.Pre-treatment period: patients will undergo screening for protocol eligibility within 28 days (4weeks) prior to randomization.

Subjects who meet all the inclusion criteria will be randomized based on a computer-generated randomization schedule prepared by the Coordinating Centre. The first randomization will occur for the induction treatment: Arm A (Rd) or B (MPR) or C (CPR). Within each arm patients will be then randomized for the maintenance treatment(lenalidomide or lenalidomide and prednisone): Arms A1 (R) and A2 (RP); Arms B1 (R) and B2 (RP); Arms C1 (R) and C2 (RP). Randomization will be concealed until the end of the induction period for the maintenance treatment. Patients will be stratified at randomization according to the International Staging System (5) and age (< 75 years vs > 75 years).Treatment period includes induction and maintenance. During the induction and maintenance phases, all patients will attend periodic study center visits in order to asses the safety and efficacy of the treatment. This protocol also provides a substudy designed to observe asymptomatic patients excluded to the protocol that in any case could be inserted in the study . The asymptomatic patient is characterized by the absence of end-organ damage or tissue involvement, such as anemia, bone lesions, hypercalcemia, and renal failure, or by other relevant clinical conditions, such as hyperviscosity, amyloidosis, and recurrent infections (CRAB).

Being tested
Melphalan, Prednisone, Lenalidomide, Cyclophosphamide, Prednisone, Lenalidomide, Lenalidomide, dexamethasone
Keywords
Multiple Myeloma, Elderly Patients, Diagnosis, Lenalidomide, Prednisone, Melphalan, Dexamethasone, Cyclophosphamide
Medical subject headings
Multiple Myeloma, Disease

What participants receive

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

  • Melphalan, Prednisone, LenalidomideDrug

    Induction: 9 courses every 28 days - oral Lenalidomide for 21 days followed by a 7 days rest period; oral Melphalan for 4 days, followed by a 24 days rest period [different doses according to the age of patients (65-75 or >75 years old);oral Prednisone for 4 days followed by a 24 day rest period.

    Maintenance: ARM A1, B1 and C1 - oral Lenalidomide on day 1-21 followed by a 7 days rest period.

    ARM A2,B2 and C2:oral Lenalidomide on day 1-21 followed by a 7 days rest period and oral Prednisone every other day.Each cycle will be repeated every 28 days, until any sign of disease progression(PD).

  • Cyclophosphamide, Prednisone, LenalidomideDrug

    Induction: 9 cycles every 28 days:Lenalidomide will be given orally at the dose of 25 mg/day for 21 days followed by a 7 days rest period (day 22 to 28;Cyclophosphamide will be given orally at the dose of 50 mg /day for 21 days followed by a 7 day rest period (days 1 to 28) in patients 65-75 years old and 50 mg every other day (days 1 to 20 followed by a 8 days rest period [day 21 to 28]) in patients older than 75 years.Prednisone will be given orally at the dose of 25 mg every other day (days 1 to 28.Each cycle will be repeated every 28 days, until any sign of disease progression(PD).

  • Lenalidomide, dexamethasoneDrug

    Induction: 9 course every 28 days-Lenalidomide will be given orally at the dose of 25 mg/day for 21 days followed by a 7 days rest period (day 22 to 28); Dexamethasone will be given orally at the dose of 40 mg on days 1, 8, 15 and 22 every 28 days in patients 65-75 years old and at the dose of 20 mg on days 1,8,15 and 22 every 28 days in patients older than 75 years. Maintenance:After 2-3 months from the completion of the last induction cycle, patients will start maintenance therapy according to physician willing and general dose-reduction rules.ARM A1, B1 and C1:Lenalidomide will be given at the dose of 10 mg/day on day 1-21 followed by a 7 days rest period. ARM A2, B2 and C2:Lenalidomide will be given at the dose of 10 mg/day on day 1-21 followed by a 7 days rest period; Prednisone will be given orally at the dose of 25 mg every other day (days 1 to 28) Each cycle will be repeated every 28 days, until any sign of disease progression (PD).

Study groups in NCT01093196
Study groupRoleWhat they receive
RdActive comparatorInduction treatment with oral Lenalidomide and low dose dexamethasone followed by maintenance therapy with Lenalidomide alone or Lenalidomide and Prednisone
Receives: Drug: Lenalidomide, dexamethasone
MPRExperimentalInduction treatment with oral Lenalidomide, Prednisone and Melphalan followed by maintenance therapy with Lenalidomide alone or Lenalidomide and Prednisone
Receives: Drug: Melphalan, Prednisone, Lenalidomide
CPRExperimentalInduction treatment with oral Lenalidomide, Cyclophosphamide and Prednisone for followed by maintenance therapy with Lenalidomide alone or Lenalidomide and Prednisone.
Receives: Drug: Cyclophosphamide, Prednisone, Lenalidomide

What is being measured

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

  1. Progression Free Survival

    Measured: 5 years

Secondary outcomes (7)

  1. Overall Survival

    Measured: 5 years

  2. Overall Response Rate

    Measured: 5 years

  3. Time to progression

    Measured: 5 years

  4. Time and duration of response

    Measured: 5 years

  5. Time to next therapy

    Measured: 5 years

  6. Grade 3-4 hematological and non-hematological adverse events (AEs)

    Measured: 5 years

  7. Prognosis and cytogenetic abnormalities

    Measured: 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 posted25 Mar 2010 (estimated)
  2. Study startOct 2009
  3. Primary completionNov 2012
  4. Study completion1 Jul 2024

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
660 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01093196
Sponsor's protocol ID
EMN01
Status last verified
Nov 2024
First submitted
24 Mar 2010
Last updated
7 Nov 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • Bringhen S, D'Agostino M, Paris L, Ballanti S, Pescosta N, Spada S, Pezzatti S, Grasso M, Rota-Scalabrini D, De Rosa L, Pavone V, Gazzera G, Aquino S, Poggiu M, Santoro A, Gentile M, Baldini L, Petrucci MT, Tosi P, Marasca R, Cellini C, Palumbo A, Falco P, Hajek R, Boccadoro M, Larocca A. Lenalidomide-based induction and maintenance in elderly newly diagnosed multiple myeloma patients: updated results of the EMN01 randomized trial. Haematologica. 2020 Jul;105(7):1937-1947. doi: 10.3324/haematol.2019.226407. Epub 2019 Oct 3.

    PubMed 31582542

  • Larocca A, Mina R, Offidani M, Liberati AM, Ledda A, Patriarca F, Evangelista A, Spada S, Benevolo G, Oddolo D, Innao V, Cangiolosi C, Bernardini A, Musto P, Amico V, Fraticelli V, Paris L, Giuliani N, Falcone AP, Zambello R, De Paoli L, Romano A, Palumbo A, Montefusco V, Hajek R, Boccadoro M, Bringhen S. First-line therapy with either bortezomib-melphalan-prednisone or lenalidomide-dexamethasone followed by lenalidomide for transplant-ineligible multiple myeloma patients: a pooled analysis of two randomized trials. Haematologica. 2020 Apr;105(4):1074-1080. doi: 10.3324/haematol.2019.220657. Epub 2019 Jun 27.

    PubMed 31248973

  • Montefusco V, Gay F, Spada S, De Paoli L, Di Raimondo F, Ribolla R, Musolino C, Patriarca F, Musto P, Galieni P, Ballanti S, Nozzoli C, Cascavilla N, Ben-Yehuda D, Nagler A, Hajek R, Offidani M, Liberati AM, Sonneveld P, Cavo M, Corradini P, Boccadoro M. Outcome of paraosseous extra-medullary disease in newly diagnosed multiple myeloma patients treated with new drugs. Haematologica. 2020 Jan;105(1):193-200. doi: 10.3324/haematol.2019.219139. Epub 2019 Jun 20.

    PubMed 31221778

  • Magarotto V, Bringhen S, Offidani M, Benevolo G, Patriarca F, Mina R, Falcone AP, De Paoli L, Pietrantuono G, Gentili S, Musolino C, Giuliani N, Bernardini A, Conticello C, Pulini S, Ciccone G, Maisnar V, Ruggeri M, Zambello R, Guglielmelli T, Ledda A, Liberati AM, Montefusco V, Hajek R, Boccadoro M, Palumbo A. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. Blood. 2016 Mar 3;127(9):1102-8. doi: 10.1182/blood-2015-08-662627. Epub 2016 Jan 4.

    PubMed 26729895

  • Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BG, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015 Mar 26;125(13):2068-74. doi: 10.1182/blood-2014-12-615187. Epub 2015 Jan 27.

    PubMed 25628469

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Melphalan, Prednisone, Lenalidomide, Cyclophosphamide, Prednisone, Lenalidomide and Lenalidomide, dexamethasone in people with Multiple Myeloma, run by Fondazione EMN Italy Onlus 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 38 inclusion and 4 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 7 Nov 2024. 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?

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?

Progression Free Survival (time frame: 5 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 NCT01093196, which also lists 5 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 7 Nov 2024.

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