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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide; Drug: Adriamycin; Drug: Dexamethasone

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Patra, Greece, 26504
    • University General Hospital of Patras
  • Thessaloniki, Greece, 54007
    • Theageneio Anticancer Hospital of Thessaloniki
  • Attica
    • Athens, Attica, Greece, 11528
      • General Hospital of Athens "Alexandra"
    • Athens, Attica, Greece, 11527
      • General Hospital of Athens "G. Gennimatas"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

1

Arms and Interventions

Participant Group / Arm

Intervention / 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

Drug: Lenalidomide; Lenalidomide 25 mg by mouth for the first 21 days of a 28-day-cycle for 4 cycles; Other Names: Combination of Lenalidomide, adriamycin & dexamethasone; Drug: Adriamycin; 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: Combination of Lenalidomide, adriamycin & dexamethasone; Drug: Dexamethasone; 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: Combination of Lenalidomide, adriamycin & dexamethasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	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	142 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)		142 days
Time to progression (TTP)		142 days
Time to Next Therapy (TtNT)		142 days
Number and severity of Adverse events as a measure of safety and toxicity profile	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

Outcome Measure	Measure Description	Time Frame
Number of stem cell collected before Autologous Stem Cell Transplantation (ASCT)		142 days
Dickkopf-1 (DKK-1)	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
Dickkopf-1 (DKK-1)	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)	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
C-telopeptide of type-I collagen (CTX)	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)	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 days
Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b)	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)	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
Bone-alkaline phosphatase (bALP)	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)	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
Osteocalcin (OC)	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)	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
C-terminal propeptide of procollagen type-I (CICP)	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)	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)	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)	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
Osteoprotegerin (OPG)	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)	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)	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)	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)	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	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
Angiopoietin-1 & -2	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	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	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	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)	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	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	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)	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)	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: Meletios A. Dimopoulos
• 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: November 1, 2014
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: June 5, 2015
• First Submitted That Met QC Criteria: June 10, 2015
• First Posted (Estimate): June 15, 2015

Study Record Updates

• Last Update Posted (Estimate): October 17, 2016
• Last Update Submitted That Met QC Criteria: October 14, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Multiple Myeloma
• 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: RV-MM-GMSG-392; 2011-001499-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided