Lenalidomide & Adriamycin & Dexamethasone (RAD) in Newly Diagnosed, Multiple Myeloma Patients (RAD)
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 Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Actual)
Enrollment
Phase
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Patra, Greece, 26504
- University General Hospital of Patras
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Thessaloniki, Greece, 54007
- Theageneio Anticancer Hospital of Thessaloniki
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Attica
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Athens, Attica, Greece, 11528
- General Hospital of Athens "Alexandra"
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Athens, Attica, Greece, 11527
- General Hospital of Athens "G. Gennimatas"
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Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Subjects able to read and understand the Informed Consent Form (ICF).
- Subjects willing to participate in the study and comply with its procedures.
- Subjects who have signed the ICF
- Newly diagnosed patients with symptomatic MM according to the criteria of IMWG
- Subjects eligible for autologous stem cell transplantation
- Age 18-70 years, of either sex
- karnofsky ≥ 60
- Platelets ≥ 100x109/L
- Neutrophils ≥ 1.5x109/L
- Alanine transaminase (ALT) & Aspartate transaminase (AST) ≤ 3-fold of upper normal limit
- Bilirubin ≤ 2-fold of upper normal limit
- Creatinine clearance ≥60 ml/min
- Expected survival ≥ 6 months as per PI's clinical judgment
- Subjects able to tolerate aspirin, low molecular weight heparin or coumarinic agents as prophylactic anticoagulation
- 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.
- 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.
- Subjects must be free of any clinically significant disease (other than MM) that would interfere with study evaluations
Exclusion Criteria:
- Pregnancy, breastfeeding οr intention of pregnancy during the trial
- Suspected or known hypersensitivity to any of the study drugs
- Ongoing severe infection requiring intravenous antibiotic treatment
- 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
- Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
- 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
- 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
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the ICF
- 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
- Subjects with any clinical condition that would affect study's outcome
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: Lenalidomide, adriamycin & dexamethasone
Lenalidomide 25 mg administered orally for the first 21 days of each 28-day-cycle, plus Adriamycin i.v. on days 1,2,3 & 4 of every cycle, plus Dexamethasone 40 mg orally on days 1, 8, 15 & 22 of every cycle for 4 cycles
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Lenalidomide 25 mg by mouth for the first 21 days of a 28-day-cycle for 4 cycles
Other Names:
Adriamycin as intravenous bolus infusion at a dose of 9 mg/m2, on days 1-4 of a 28-day cycle for 4 cycles
Other Names:
Dexamethasone by mouth at a dose of 40 mg, on days 1, 8, 15, and 22 of a 28-day cycle for 4 cycles
Other Names:
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What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Overall response rate
Time Frame: 142 days
|
Assessment of the overall response rate of study population to RAD regimen (including stringent complete response, complete response, very good partial response, partial response and stable disease) according to the uniform criteria of IMWG (International Myeloma Working Group) regarding the response to multiple myeloma therapy
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142 days
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Progression-free survival (PFS)
Time Frame: 142 days
|
142 days
|
|
|
Time to progression (TTP)
Time Frame: 142 days
|
142 days
|
|
|
Time to Next Therapy (TtNT)
Time Frame: 142 days
|
142 days
|
|
|
Number and severity of Adverse events as a measure of safety and toxicity profile
Time Frame: 142 days
|
Adverse events will be assessed at each visit and graded according to the National Cancer Institute Common Toxicity Criteria (version 2.0)
|
142 days
|
Other Outcome Measures
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Number of stem cell collected before Autologous Stem Cell Transplantation (ASCT)
Time Frame: 142 days
|
142 days
|
|
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Dickkopf-1 (DKK-1)
Time Frame: 1 day
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Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
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1 day
|
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Dickkopf-1 (DKK-1)
Time Frame: 112 days
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
C-telopeptide of type-I collagen (CTX)
Time Frame: 1 day
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
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1 day
|
|
C-telopeptide of type-I collagen (CTX)
Time Frame: 112 days
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)
Time Frame: 1 days
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Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
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1 days
|
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Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)
Time Frame: 112 days
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
Bone-alkaline phosphatase (bALP)
Time Frame: 1 day
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Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
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1 day
|
|
Bone-alkaline phosphatase (bALP)
Time Frame: 112 days
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
Osteocalcin (OC)
Time Frame: 1 day
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Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
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1 day
|
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Osteocalcin (OC)
Time Frame: 112 days
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
C-terminal propeptide of procollagen type-I (CICP)
Time Frame: 1 day
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Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
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1 day
|
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C-terminal propeptide of procollagen type-I (CICP)
Time Frame: 112 days
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
Soluble and total RANKL (sRANKL, tRANKL)
Time Frame: 1 day
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Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
1 day
|
|
Soluble and total RANKL (sRANKL, tRANKL)
Time Frame: 112 days
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
Osteoprotegerin (OPG)
Time Frame: 1 day
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
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1 day
|
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Osteoprotegerin (OPG)
Time Frame: 112 days
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
Osteopontin (OPN)
Time Frame: 1 day
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Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
1 day
|
|
Osteopontin (OPN)
Time Frame: 112 days
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
Macrophage inflammatory protein 1-alpha (MIP-1α)
Time Frame: 1 day
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
1 day
|
|
Macrophage inflammatory protein 1-alpha (MIP-1α)
Time Frame: 112 days
|
Biochemical markers of bone remodeling will be measured in the serum of patients at therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
Angiopoietin-1 & -2
Time Frame: 1 day
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Angiogenic cytokines, which will be evaluated in the serum of patients during therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
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1 day
|
|
Angiopoietin-1 & -2
Time Frame: 112 days
|
Angiogenic cytokines, which will be evaluated in the serum of patients during therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
Angiogenin
Time Frame: 1 day
|
Angiogenic cytokines, which will be evaluated in the serum of patients during therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
1 day
|
|
Angiogenin
Time Frame: 112 days
|
Angiogenic cytokines, which will be evaluated in the serum of patients during therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
VEGF
Time Frame: 1 day
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Angiogenic cytokines, which will be evaluated in the serum of patients during therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
1 day
|
|
Vascular endothelial growth factor (VEGF)
Time Frame: 112 days
|
Angiogenic cytokines, which will be evaluated in the serum of patients during therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
VEGF-A
Time Frame: 1 day
|
Angiogenic cytokines, which will be evaluated in the serum of patients during therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
1 day
|
|
VEGF-A
Time Frame: 112 days
|
Angiogenic cytokines, which will be evaluated in the serum of patients during therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
|
basic fibroblast growth factor (bFGF)
Time Frame: 1 day
|
Angiogenic cytokines, which will be evaluated in the serum of patients during therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
1 day
|
|
basic fibroblast growth factor (bFGF)
Time Frame: 112 days
|
Angiogenic cytokines, which will be evaluated in the serum of patients during therapy commencement on Day 1 of cycle 1 and at therapy completion on day 28 of cycle 4. 28-days-cycle
|
112 days
|
Collaborators and Investigators
Sponsor
Sponsor
Investigators
Investigators
- Principal Investigator: Meletios Dimopoulos, Doctor, General Hospital of Athens "Alexandra"
- Principal Investigator: Eirini Katodritou, Doctor, Theageneio Anticancer Hospital of Thessaloniki
- Principal Investigator: Nikolaos Anagnostopoulos, Doctor, General Hospital of Athens "G. Gennimatas''
- Principal Investigator: Argirios Symeonidis, Doctor, University General Hospital of Patras
Study record dates
Study Major Dates
Study Start
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Estimate)
First Posted
Study Record Updates
Last Update Posted (Estimate)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Antibiotics, Antineoplastic
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Lenalidomide
- Doxorubicin
- Liposomal doxorubicin
Other Study ID Numbers
Other Study ID Numbers
- RV-MM-GMSG-392
- 2011-001499-20 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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