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Elotuzumab, Lenalidomide and Dexamethasone in Treatment of Transplant-Eligible Newly Diagnosed Multiple Myeloma Patients

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ClinicalTrials.gov Identifier: NCT02843074
Recruitment Status : Active, not recruiting
First Posted : July 25, 2016
Last Update Posted : September 17, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief Summary:
This is a phase 2, single arm, open-label, multicenter study to evaluate the feasibility and tolerance of the combination of elotuzumab, lenalidomide, and dexamethasone in the induction, consolidation, and maintenance treatment of transplant eligible, newly diagnosed multiple myeloma patients.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: elotuzumab Drug: Lenalidomide Drug: Dexamethasone Procedure: autologous stem cell transplantation Phase 2

Detailed Description:

The primary purpose of this study is to evaluate the feasibility of using the combination of elotuzumab, lenalidomide, and dexamethasone (ERd) as induction therapy and the ability of the combination to facilitate the start of autologous stem cell transplantation (ASCT) in transplant-eligible patients newly diagnosed with multiple myeloma. In addition to induction, the efficacy, safety, and tolerability of ERd as consolidation and maintenance therapy in these patients will be observed.

Eligible patients will undergo four 28-day cycles of an induction regimen of elotuzumab, lenalidomide, and dexamethasone. Following completion of 4 cycles of induction therapy, all patients will undergo standard mobilization, collection of stem cells, and then ASCT using a melphalan conditioning regimen as per institutional guidelines.

Toxicity evaluation will be interrupted during the stem cell procedure and will resume with the onset of consolidation. Adverse events will be collected, however, from the end of induction up to mobilization.

Consolidation therapy will begin 70 to 120 days following ASCT and will consist of four 28-day cycles of elotuzumab, lenalidomide, and dexamethasone. All patients that do not experience progressive disease will begin maintenance therapy of elotuzumab, lenalidomide, and dexamethasone. The duration of maintenance will be 24 months.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study Assessing Feasibility and Tolerance of the Combination of Elotuzumab, Lenalidomide and Dexamethasone in Induction, Consolidation and Maintenance Treatment of Transplant-Eligible Patients Newly Diagnosed With Multiple Myeloma
Actual Study Start Date : September 21, 2016
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : March 2022


Arm Intervention/treatment
Experimental: ERd Therapy

INDUCTION:

Cycles 1-2: elotuzumab 10mg/kg IV days 1, 8, 15, 22; lenalidomide (len) 25mg orally (PO), once daily (QD) on days 1-21; dexamethasone (dex) 28 mg PO (3-24 hrs before elotuzumab IV) and 8mg IV (45-90 minutes before elotuzumab) days 1, 8, 15, 22.

Cycles 3-4: elotuzumab 10mg/kg IV days 1 and 15; len 25mg PO QD days 1-21; dex 8mg PO (3-24 hrs before elotuzumab IV) and 8mg IV (45-90 minutes before elotuzumab) days 1 and 15; dex 40mg PO days 8 and 22.

CONSOLIDATION:

Four 28-day cycles: elotuzumab 10mg/kg IV days 1 and 15; len 15mg PO QD days 1-21; dex 28mg PO (3-24 hrs before elotuzumab) and 8mg IV (45-90 minutes before elotuzumab) days 1 and 15; dex 40mg PO days 8 and 22.

MAINTENANCE:

After completing consolidation therapy patients without progressive disease will receive, for up to 24 months, 28-day cycles of elotuzumab 20mg/kg IV day 1; len 10mg +/- 5mg PO QD days 1-21; dex 28mg PO (3-24 hrs before elotuzumab) and 8mg IV (45-90 minutes prior to elotuzumab) day 1.

Drug: elotuzumab
Given intravenously (IV)
Other Name: Empliciti

Drug: Lenalidomide
Given by IV
Other Name: Revlimid

Drug: Dexamethasone
Given orally (PO) or by IV
Other Name: Decadron

Procedure: autologous stem cell transplantation
Other Name: ASCT




Primary Outcome Measures :
  1. Induction Feasibility Rate (IFR) [ Time Frame: weekly for 16 weeks ]
    Defined as the percentage of patients who successfully complete four 28-day cycles of induction therapy with elotuzumab, lenalidomide and dexamethasone (ERd) and are able to start autologous stem cell transplantation (ASCT).


Secondary Outcome Measures :
  1. Complete Response Rate (CRR) [ Time Frame: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years ]
    Defined as the percentage of patients who achieve a complete response (CR) or near complete response (nCR) to treatment at each stage of the study (induction, ASCT, consolidation, end of study) per International Myeloma Working Group (IMWG) and European Group for Blood and Marrow Transplantation (EBMT) criteria.

  2. Overall Response Rate (ORR) [ Time Frame: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years ]
    Defined as the percentage of patients who achieve at least a partial response (PR) to treatment at each stage of the study (induction, ASCT, consolidation, end of study) per IMWG and EBMT criteria

  3. Progression-free survival (PFS) [ Time Frame: every 4 weeks until end of treatment visit, and every 3 months thereafter up to 3 years ]
    Defined as the time from start of induction treatment to documented progressive disease (PD) or death from any cause up to 3 years post first study treatment

  4. Overall survival (OS) [ Time Frame: every 4 weeks until end of treatment visit, and up to 3 years thereafter ]
    Defined as the time from start of induction treatment to 3 years post first study treatment or death from any cause, whichever comes first

  5. The number of treatment-emergent adverse events, serious adverse events, deaths as a measure of safety [ Time Frame: weekly for 8 weeks, then every 2 weeks till start of mobilization and 70-120 days post-ASCT ]
    Safety data and abnormal lab values will be collected and assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE V4.03) and abnormal vital signs.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed myeloma requiring systemic chemotherapy as per International Myeloma Working Group (IMWG) uniform criteria and Diagnostic Criteria and Staging for Multiple Myeloma

    • Ideally, no prior therapy, or
    • No more than 1 cycle of therapy for emergent control of disease prior to enrolling on study, including prior treatment of hypercalcemia, spinal cord compression, or active and/or aggressively progressing myeloma with corticosteroids or lenalidomide or bortezomib-based regimens (treatment dose should not exceed the equivalent of 160 mg of dexamethasone in a 4 week period, or not more than 1 cycle)
    • Bisphosphonates are permitted
  • Eligible and plan to undergo ASCT in first remission
  • Measurable disease, prior to initial treatment as indicated by one or more of the following:

    • Serum M-protein ≥1.0 g/dL
    • Urine M-protein ≥200 mg/24 hours
    • Serum free light chain assay: involved free light chain level ≥10 mg/dL (≥100 mg/L) provided the serum free light chain ratio is abnormal.
  • Ability to take aspirin or other venous thromboembolism (VTE) anticoagulant therapy
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 thru 2
  • Adequate hematologic, renal, and liver function.
  • All study participants must be registered into the mandatory Revlimid REMS® program and must be willing and able to comply with the requirements of that program.
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
  • Male patients with female partners of childbearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 28 days following last dose of study drugs. Male patients must also refrain from donating semen or sperm during their participation in the study.
  • Willingness and ability to comply with study and follow-up procedures.
  • Ability to understand the nature of this study and give written informed consent.

Exclusion Criteria:

  • Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome
  • Plasma cell leukemia
  • Waldenström's macroglobulinemia or IgM myeloma
  • Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with a history of non-melanoma skin cancer.
  • Radiotherapy to multiple sites or immunotherapy within 4 weeks before start of protocol treatment (localized radiotherapy to a single site at least 1 week before start is permissible)
  • Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement.
  • Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose of study treatment
  • Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade ≥2, and malabsorption syndrome)
  • Any of the following cardiac diseases currently or within the last 6 months:

    • Left ventricular ejection fraction (LVEF) <40% as determined by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan
    • Unstable angina pectoris
    • Congestive heart failure (New York Heart Association ≥ Grade 2
    • Acute myocardial infarction
    • Conduction abnormality not controlled with pacemaker or medication
    • Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
    • Valvular disease with significant compromise in cardiac function
  • Known seropositive for or active viral infection with human immunodeficiency virus or hepatitis A, B, or C virus. Patients who are seropositive because of hepatitis B virus vaccine are eligible.
  • Any clinically significant medical disease or condition that, in the treating Investigator's opinion, may interfere with protocol adherence or a patient's ability to give informed consent
  • Pregnant or lactating females
  • Contraindication to any of the required concomitant drugs, including dexamethasone, H1 and H2 blockers, and acetaminophen, or if patient has a history of prior thrombotic disease, warfarin or low molecular weight heparin
  • No health coverage, or if the copay for lenalidomide is not acceptable to the patient.
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02843074


Locations
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United States, Colorado
Colorado Blood Cancer Institute
Denver, Colorado, United States, 80218
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Missouri
HCA Midwest Health/Research Medical Center
Kansas City, Missouri, United States, 64132
United States, Nebraska
Nebraska Methodist Hospital
Omaha, Nebraska, United States, 68114
United States, Tennessee
Tennessee Oncology
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
SCRI Development Innovations, LLC
Bristol-Myers Squibb
Investigators
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Study Chair: Jesus Berdeja, MD SCRI Development Innovations, LLC

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Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT02843074     History of Changes
Other Study ID Numbers: SCRI MM61
First Posted: July 25, 2016    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by SCRI Development Innovations, LLC:
B-cell tumors
autologous stem cell transplantation
blood cancers
Additional relevant MeSH terms:
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Lenalidomide
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
Dexamethasone
Dexamethasone acetate
Elotuzumab
BB 1101
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
Antineoplastic Agents