Lenalidomide and Dexamethasone Versus Melphalan Prednisone and Lenalidomide Versus Cyclophosphamide, Prednisone and Lenalidomide in Elderly Multiple Myeloma Patients
Information source: Fondazione Neoplasie Sangue Onlus
Information obtained from ClinicalTrials.gov on February 07, 2013
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multiple Myeloma
Intervention: Melphalan, Prednisone, Lenalidomide (Drug); Cyclophosphamide, Prednisone, Lenalidomide (Drug); Lenalidomide, dexamethasone (Drug)
Phase: Phase 3
Sponsored by: Fondazione Neoplasie Sangue Onlus
Official(s) and/or principal investigator(s):
Antonio Palumbo, MD, Principal Investigator, Affiliation: Division of Hematology, A.O.U. San Giovanni Battista
Antonio Palumbo, MD, Phone: +39 011 633, Ext: 4260, Email: email@example.com
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
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Progression Free Survival
Overall Response Rate
Time to progression
Time and duration of response
Time to next therapy
Grade 3-4 hematological and non-hematological adverse events (AEs)
Prognosis and cytogenetic abnormalities
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
Minimum age: 18 Years.
Maximum age: N/A.
- Patient is, in the investigator(s) opinion, willing and able to comply with the
- 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
- 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*
- 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
- 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
- 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)
Locations and Contacts
Antonio Palumbo, MD, Phone: +39 011 633, Ext: 4260, Email: firstname.lastname@example.org
Division Of Hematology, A.O.U. San Giovanni Battista, Torino, TO 10126, Italy; Recruiting
Starting date: October 2009
Last updated: December 28, 2011