Clinical trial NCT02471820: Lenalidomide & Adriamycin & Dexamethasone (RAD) in Newly Diagnosed, Multiple Myeloma Patients
Official title: Phase II Open Label Study for the Assessment of the Efficacy and Safety of Lenalidomide & Adriamycin & Low Dose Dexamethasone (RAD) in Newly Diagnosed, Symptomatic Multiple Myeloma Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Lead sponsor: University of Athens
Sponsor class: OTHER
First posted: 2015-06-15
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is to assess the efficacy and safety of lenalidomide in combination with adriamycin and low dose dexamethasone in newly diagnosed patients with symptomatic multiple myeloma as well as to collect information regarding the effect of this regimen on angiogenesis and bone remodeling of the study population.

Detailed description: This is a Phase II, non randomized, non- comparative, open label trial which assess the efficacy and safety of lenalidomide, adriamycin and low dose dexamethasone combination (RAD) in 45 newly diagnosed patients with symptomatic multiple myeloma as well as to collect information regarding the effect of this regimen on angiogenesis and bone remodeling of the study population. The recruitment period is estimated for 5 months while the treatment period and the follow up period 4 months and 1 month respectively. During the treatment initiation visit the response to the combination RAD according the International Myeloma Working Group (IMWG) criteria will be evaluated, biochemical markers of bone metabolism and angiogenic cytokines will be measured as well. IMWG Response evaluation will be repeated the day 1 of each treatment cycle as well as at the response evaluation visit. Finally biochemical markers of bone metabolism and angiogenic cytokines will be measured once more at the end of treatment visit.

Eligibility criteria: Inclusion Criteria:

1. Subjects able to read and understand the Informed Consent Form (ICF).
2. Subjects willing to participate in the study and comply with its procedures.
3. Subjects who have signed the ICF
4. Newly diagnosed patients with symptomatic MM according to the criteria of IMWG
5. Subjects eligible for autologous stem cell transplantation
6. Age 18-70 years, of either sex
7. karnofsky ≥ 60
8. Platelets ≥ 100x109/L
9. Neutrophils ≥ 1.5x109/L
10. Alanine transaminase (ALT) \& Aspartate transaminase (AST) ≤ 3-fold of upper normal limit
11. Bilirubin ≤ 2-fold of upper normal limit
12. Creatinine clearance ≥60 ml/min
13. Expected survival ≥ 6 months as per PI's clinical judgment
14. Subjects able to tolerate aspirin, low molecular weight heparin or coumarinic agents as prophylactic anticoagulation
15. Female subject of childbearing potential must have 2 negative serum pregnancy tests (hCG) at Screening (once within 10-14 days and once 24 h before the study drug administration) and if sexually active must be using two medically acceptable, highly effective, adequate forms of birth control (ie, failure rate \<1% per year when used consistently and correctly) prior to Screening and and for time period at least 28 days before the study drug administration and agree to continue using it while being in the study (Screening and Treatment Periods including dose interruptions). A female subject should continue using a highly effective method of birth control for 30 days following the end of treatment.
16. A male subject must agree to use an adequate form of contraception for the duration of the study, while taking the study drug, during dose interruptions at for at least 28 days after the last dose of study drug even if he has had a successful vasectomy and agree to have sexual relations only with women who use a highly effective birth control method.
17. Subjects must be free of any clinically significant disease (other than MM) that would interfere with study evaluations

Exclusion Criteria:

1. Pregnancy, breastfeeding οr intention of pregnancy during the trial
2. Suspected or known hypersensitivity to any of the study drugs
3. Ongoing severe infection requiring intravenous antibiotic treatment
4. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 5 years. Concurrent prostate cancer for which the patient is receiving therapy will not be considered an exclusion if the Prostatic specific antigen (PSA) has been stable for 3 years
5. Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
6. Myocardial infraction within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmia, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
7. Uncontrolled medical problems such as diabetes, coronary artery disease, hypertension, unstable angina, arrhythmia, pulmonary, hepatic and renal diseases unless renal insufficiency is considered to be secondary to MM
8. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the ICF
9. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she will participate in the study or confounds the ability to interpret data from the study
10. Subjects with any clinical condition that would affect study's outcome
11. Participation in another interventional clinical trial in the 4 weeks preceding enrollment or planning to participate in another interventional clinical trial during the planned period of this study, except of the clinical trials that implicate drugs of supportive treatment

Primary outcomes:
measure: Overall response rate
timeFrame: 142 days
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: 142 days
measure: Time to progression (TTP)
timeFrame: 142 days
measure: Time to Next Therapy (TtNT)
timeFrame: 142 days
measure: Number and severity of Adverse events as a measure of safety and toxicity profile
timeFrame: 142 days
Other outcomes:
measure: Number of stem cell collected before Autologous Stem Cell Transplantation (ASCT)
timeFrame: 142 days
measure: Dickkopf-1 (DKK-1)
timeFrame: 1 day
measure: Dickkopf-1 (DKK-1)
timeFrame: 112 days
measure: C-telopeptide of type-I collagen (CTX)
timeFrame: 1 day
measure: C-telopeptide of type-I collagen (CTX)
timeFrame: 112 days
measure: Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)
timeFrame: 1 days
measure: Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)
timeFrame: 112 days
measure: Bone-alkaline phosphatase (bALP)
timeFrame: 1 day
measure: Bone-alkaline phosphatase (bALP)
timeFrame: 112 days
measure: Osteocalcin (OC)
timeFrame: 1 day
measure: Osteocalcin (OC)
timeFrame: 112 days
measure: C-terminal propeptide of procollagen type-I (CICP)
timeFrame: 1 day
measure: C-terminal propeptide of procollagen type-I (CICP)
timeFrame: 112 days
measure: Soluble and total RANKL (sRANKL, tRANKL)
timeFrame: 1 day
measure: Soluble and total RANKL (sRANKL, tRANKL)
timeFrame: 112 days
measure: Osteoprotegerin (OPG)
timeFrame: 1 day
measure: Osteoprotegerin (OPG)
timeFrame: 112 days
measure: Osteopontin (OPN)
timeFrame: 1 day
measure: Osteopontin (OPN)
timeFrame: 112 days
measure: Macrophage inflammatory protein 1-alpha (MIP-1α)
timeFrame: 1 day
measure: Macrophage inflammatory protein 1-alpha (MIP-1α)
timeFrame: 112 days
measure: Angiopoietin-1 & -2
timeFrame: 1 day
measure: Angiopoietin-1 & -2
timeFrame: 112 days
measure: Angiogenin
timeFrame: 1 day
measure: Angiogenin
timeFrame: 112 days
measure: VEGF
timeFrame: 1 day
measure: Vascular endothelial growth factor (VEGF)
timeFrame: 112 days
measure: VEGF-A
timeFrame: 1 day
measure: VEGF-A
timeFrame: 112 days
measure: basic fibroblast growth factor (bFGF)
timeFrame: 1 day
measure: basic fibroblast growth factor (bFGF)
timeFrame: 112 days
Locations:
city: Athens
country: Greece
facility: General Hospital of Athens "G. Gennimatas"
state: Attica
city: Athens
country: Greece
facility: General Hospital of Athens "Alexandra"
state: Attica
city: Patra
country: Greece
facility: University General Hospital of Patras
city: Thessaloniki
country: Greece
facility: Theageneio Anticancer Hospital of Thessaloniki
Study officials:
affiliation: General Hospital of Athens "Alexandra"
name: Meletios Dimopoulos, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Theageneio Anticancer Hospital of Thessaloniki
name: Eirini Katodritou, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: General Hospital of Athens "G. Gennimatas''
name: Nikolaos Anagnostopoulos, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: University General Hospital of Patras
name: Argirios Symeonidis, Doctor
role: PRINCIPAL_INVESTIGATOR
References: