Study of Bortezomib,Lenalidomide,Dexamethasone & Elotuzumab in Newly Diagnosed MM

NCT02375555 | Completed Phase 2 Results DMC

• 1 other identifier: 14-453
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

This research study is evaluating a combination of four drugs -- lenalidomide, bortezomib, dexamethasone and elotuzumab -- as therapy for newly diagnosed multiple myeloma.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 4 Cycle Response Rate

  Disease response was defined as the proportion of patients who achieved a response of partial response or better using International Myeloma Working Group (IMWG) response criteria. Partial Response (PR) defined as 50% reduction of serum M-protein and reduction in 24h urinary M-protein by ≥90% or to \<200mg/24h; Very Good Partial Response (VGPR) defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level \<100mg/24h; Complete Response (CR) defined as negative immunofixation on serum and urine and, disappearance of any soft tissue plasmacytomas and, \<5% plasma cells in BM; Stringent Complete Response (sCR) defined as normal FLC ratio and absence of clonal cells in BM by immunohistochemistry or 2-4 color flow cytometry. The Clopper and Pearson method was used to estimate the 95% CIs for the response rate at Week 12.

  Participants were followed up to 12 weeks.

Secondary Outcomes (6)

• Successful Stem Cell Mobilization (SC Mob) Rate

  The most distant time of stem cell mobilization from time of registration is 21.4 weeks with a median of 15.14 weeks.

• 4 Cycle Ever Dose Modification (DM) Rate

  Participants were followed up to 12 weeks.

• Grade 3 and 4 Treatment-Emergent Adverse Event (TEAE) Rate

  The adverse event observation period defined as the time on treatment (+30d) is 278 weeks.

• Best Responses to E-RVD.

  Participants were followed up to 273.6 weeks.

• Objective Response Rate (ORR) at End of 8 Cycles of Induction Therapy.

  Participants were followed up to 24 weeks.

Study Arms (1)

Elotuzumab, lenalidomide, bortezomib, and dexamethasone

EXPERIMENTAL

Participants will receive therapy with the combination of lenalidomide, bortezomib, and dexamethasone and elotuzumab (E-RVD). Induction cycles (1 to 8) are 21-day cycles. * Elotuzumab will be administered by intravenous (IV) infusion * Bortezomib as a subcutaneous injection * Lenalidomide single daily oral dose * Dexamethasone as oral tablets and IV infusion * Stem cell mobilization will be performed for all subjects at the end of Cycle 4. Subjects may elect to stop E-RVD at the end of Induction Cycle 4 and proceed to autologous SCT. Subjects who do not proceed to SCT may receive a full 8 cycles of induction therapy. The maintenance schedule (28 days) will start after 8 cycles of induction regimen for subjects not proceeding with SCT, or after recovery from SCT for subjects proceeding with it. Maintenance therapy with E-RVD will be administered to all patients, with the specific maintenance regimen determined by risk category.

Drug: Lenalidomide; Drug: Elotuzumab; Drug: Bortezomib; Drug: Dexamethasone; Procedure: Stem Cell Mobilization

Interventions

Lenalidomide DRUG

Also known as: Revlimid®

Elotuzumab, lenalidomide, bortezomib, and dexamethasone

Elotuzumab DRUG

Also known as: HuLuc63

Elotuzumab, lenalidomide, bortezomib, and dexamethasone

Bortezomib DRUG

Also known as: Velcade

Elotuzumab, lenalidomide, bortezomib, and dexamethasone

Dexamethasone DRUG

Also known as: Baycadron Elixer, Decadron

Elotuzumab, lenalidomide, bortezomib, and dexamethasone

Stem Cell Mobilization PROCEDURE

Elotuzumab, lenalidomide, bortezomib, and dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet the following criteria on screening examination to be eligible to participate in the study. All laboratory assessments should be performed within 21 days of initiation of protocol therapy unless otherwise specified.Subject is, in the investigator's opinion, willing and able to comply with the protocol requirements.
• Subject has given voluntary signed written informed consent before performance of any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (see Appendix 1).
• Subject is a candidate for high-dose therapy and autologous SCT based on standard criteria at the institution where this treatment will be administered.
• Newly diagnosed untreated, symptomatic, documented MM based on standard diagnostic criteria (Rajkumar 2009) with measurable disease, defined as any of the following:
• Serum Immunoglobulin G (IgG), Immunoglobulin (A) IgA, or Immunoglobulin M (IgM) M-protein ≥ 0.5 g/dL, or
• Serum Immunoglobulin D (IgD) M-protein ≥ 0.05 g/dL, or
• Urinary M-protein excretion of more than 200 mg/24 hours, or
• Serum free light chains (FLC) of at least 100 mg/dL with an abnormal FLC ratio
• Subject agrees to refrain from blood donations during therapy on study and for 8 weeks after therapy is completed.
• Men and women, age ≥18 years or legal age of consent per local regulations (whichever is greater).
• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting Lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking Lenalidomide through 90 days after the last dose of study drug. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy from the time of signing the informed consent form through 90 days after the last dose of study drug. All patients must be registered in and must comply with all requirements of the Revlimid Rems™ program.

You may not qualify if:

• Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.
• Diagnosed with smoldering MM, monoclonal gammopathy of undetermined significance, Waldenstrom's macroglobulinemia, Plasma cell leukemia, POEMS syndrome or amyloidosis.
• Participant has ≥ Grade 2 peripheral neuropathy on clinical examination within 21 days before initiation of protocol therapy.
• Renal insufficiency, defined as creatinine clearance \< 30 mL/min (either actual or calculated value), within 21 days of initiation of protocol therapy. The Cockgroft-Gault formula should be used for calculating creatinine clearance values:
• (140-age) x Body mass (kg) x 0.85 (female) or 1.0 (male) serum creat (mg/dL) x 72
• Ideal body weight (IBW) should be used if actual body weight is \> 20% above IBW
• Platelet count \<75,000 cells/mm3 at time of screening evaluation. Transfusion may not be used to meet platelet eligibility criteria within 7 days of obtaining screening evaluation.
• Participants with an absolute neutrophil count (ANC) \< 1000 cells/mm3 at time of screening evaluation. Growth factor may not be used to meet ANC eligibility criteria within 14 days of obtaining screening evaluation.
• Participants with hemoglobin level \< 8.0 g/dL, at time of screening. Transfusion may not be used to meet eligibility criteria within 7 days of obtaining screening evaluation.
• Participants with hepatic impairment, defined as bilirubin \> 1.5 x institutional upper limit of normal (ULN) or AST (Aspartate aminotransferase; SGOT), ALT (Alanine aminotransferase; SGPT), or alkaline phosphatase \> 3x institutional ULN, within 21 days of initiation of protocol therapy
• Other ongoing or prior anti-myeloma therapy. Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. q.d. or its equivalent) for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to study treatment.)
• Known significant cardiac abnormalities including:
• Congestive heart failure, New York Heart Association (NYHA) class III or IV
• Uncontrolled angina, arrhythmia or hypertension
• Myocardial infarction within the past six months

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Study Sites (7)

Emory University

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; elotuzumab; Bortezomib; Dexamethasone; Calcium Dobesilate; Hematopoietic Stem Cell Mobilization

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Biological Therapy; Therapeutics

Limitations and Caveats

Limitations include lack of comparator arm. Small sample size; unable to draw valid conclusions from comparison studies. Duration of follow-up was limited and longer-term assessment of patient safety is warranted. Tolerability data is limited as patient-reported outcomes data not collected.

Results Point of Contact

• Title: Ajantha Nithi
• Organization: Dana Farber Cancer Institute

ajantha_nithi@dfci.harvard.edu

857-215-2829

Study Officials

• Jacob P. Laubach, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 13, 2015
• First Posted: March 2, 2015
• Study Start: May 7, 2015
• Primary Completion: December 15, 2021
• Study Completion: January 26, 2024
• Last Updated: October 1, 2024
• Results First Posted: December 6, 2023

Record last verified: 2024-09

Locations

US (7)