Lenalidomide & Adriamycin & Dexamethasone (RAD) in Newly Diagnosed, Multiple Myeloma Patients (RAD)

• ClinicalTrials.gov Identifier: NCT02471820
• Recruitment Status: Completed
• First Posted: June 15, 2015
• Last Update Posted: October 17, 2016
• Sponsor: Meletios A. Dimopoulos
• Information provided by (Responsible Party): Meletios A. Dimopoulos, University of Athens

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Lenalidomide; Drug: Adriamycin; Drug: Dexamethasone	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: November 2014
• Actual Primary Completion Date: July 2016
• Actual Study Completion Date: July 2016

Arms and Interventions

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 Name: 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 Name: 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 Name: Combination of Lenalidomide, adriamycin & dexamethasone

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Progression-free survival (PFS) [ Time Frame: 142 days ]
2. Time to progression (TTP) [ Time Frame: 142 days ]
3. Time to Next Therapy (TtNT) [ Time Frame: 142 days ]
4. 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)

Other Outcome Measures:

1. Number of stem cell collected before Autologous Stem Cell Transplantation (ASCT) [ Time Frame: 142 days ]
2. Dickkopf-1 (DKK-1) [ 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
3. 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
4. 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
5. 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
6. Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b) [ Time Frame: 1 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
7. 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
8. Bone-alkaline phosphatase (bALP) [ 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
9. 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
10. Osteocalcin (OC) [ 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
11. 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
12. C-terminal propeptide of procollagen type-I (CICP) [ 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
13. 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
14. Soluble and total RANKL (sRANKL, tRANKL) [ 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
15. 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
16. 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
17. 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
18. Osteopontin (OPN) [ 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
19. 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
20. 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
21. 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
22. Angiopoietin-1 & -2 [ 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
23. 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
24. 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
25. 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
26. VEGF [ 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
27. 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
28. 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
29. 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
30. 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
31. 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

Eligibility Criteria

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

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

Contacts and Locations

Locations

Greece

General Hospital of Athens "G. Gennimatas"

Athens, Attica, Greece, 11527

General Hospital of Athens "Alexandra"

Athens, Attica, Greece, 11528

University General Hospital of Patras

Patra, Greece, 26504

Theageneio Anticancer Hospital of Thessaloniki

Thessaloniki, Greece, 54007

Sponsors and Collaborators

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

More Information

• Responsible Party: Meletios A. Dimopoulos, Professor of Department of Clinical Therapeutics University of Athens School of Medicine, University of Athens
• ClinicalTrials.gov Identifier: NCT02471820
• Other Study ID Numbers: RV-MM-GMSG-392; 2011-001499-20 ( EudraCT Number )
• First Posted: June 15, 2015
• Last Update Posted: October 17, 2016
• Last Verified: October 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Meletios A. Dimopoulos, University of Athens:

Multiple Myeloma

Additional relevant MeSH terms:

Dexamethasone; Dexamethasone acetate; Lenalidomide; BB 1101; Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Doxorubicin; Liposomal doxorubicin; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal