NCT02575144

Brief Summary

This phase III study, open-label, randomized study investigating lenalidomide and dexamethasone with and without biaxin in subjects with newly diagnosed, previously untreated MM. Eligible subjects will be randomized in a 1:1 ratio to receive a regimen consisting of either biaxin, lenalidomide, and low-dose dexamethasone (BiRd arm), or lenalidomide and low-dose dexamethasone (Rd arm). 306 patients will be included (50% in Spain (153) and 50% in the USA (153)

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
286

participants targeted

Target at P25-P50 for phase_3 multiple-myeloma

Timeline
Completed

Started Sep 2015

Longer than P75 for phase_3 multiple-myeloma

Geographic Reach
1 country

26 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2015

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

October 12, 2015

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 14, 2015

Completed
9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2024

Completed
Last Updated

February 1, 2022

Status Verified

January 1, 2022

Enrollment Period

9.1 years

First QC Date

October 12, 2015

Last Update Submit

January 17, 2022

Conditions

Outcome Measures

Primary Outcomes (1)

  • Progression free survival

    Throught the study. Approximately 4 years

Study Arms (2)

BiRd

EXPERIMENTAL

Subjects on the BiRD arm will receive clarithromycin, Revlimid (lenalidomide), and dexamethasone in 28-day cycles. Dosing is as follows: * Clarithromycin 500mg PO twice daily on days 1-28 for a 28-day cycle. * Lenalidomide 25mg PO daily on days 1-21 of a 28-day cycle for patients with a calculated creatinine clearance of \>60 cc/min. Patients with a calculated creatinine clearance of \<60 cc/min will receive 15 mgs PO daily on days 1-21 of a 28 cycle. * Dexamethasone 40mg PO will be given on days 1, 8, 15, 22 of a 28-day cycle.

Drug: ClarithromycinDrug: LenalidomideDrug: Dexamethasone

Rd

ACTIVE COMPARATOR

Subjects on the Rd arm will receive Revlimid, and dexamethasone in 28-day cycles. Dosing is as follows: * Lenalidomide 25mg PO daily on days 1-21 of a 28-day cycle. If a dose of lenalidomide is missed, it should be taken as soon as possible on the same day. If it is missed for the entire day, it should not be made up. Vomited doses will not be made up.Patients with renal failure will recived an ajusted dose. * Dexamethasone 40mg PO will be given on days 1, 8, 15, 22 of a 28-day cycle. Missed or vomited doses will not be made up. If subject cannot tolerate oral dexamethasone, it will be given intravenously. In patients over 75 years old, dexametasona oral will be given at dose of 20mg on days 1, 8, 15, 22 .

Drug: LenalidomideDrug: Dexamethasone

Interventions

500mg PO twice daily on days 1-28 for a 28-day cycle

BiRd

25mg PO daily on days 1-21 of a 28-day cycle for patients with a calculated creatinine clearance of \>60 cc/min

BiRdRd

40mg PO will be given on days 1, 8, 15, 22 of a 28-day cycle

BiRdRd

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Subject must voluntarily sign and understand written informed consent
  • Subject is \>=65 years at the time of signing the consent form
  • Subject has histologically confirmed MM that has never before been treated
  • Subject has no prior anti-myeloma treatment therapy within 14 days prior to initiation of study treatment except for corticosteroids with a maximum allowed dosage equivalent to three pulses of dexamethasone (40mg daily for 4 days equals one pulse). Patients may have received prior adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care, or radiation therapy as palliation for pain and/or spinal cord compression
  • Subject has measurable disease as defined by \> 0.5 g/dL serum monoclonal protein, \>10 mg/dL involved serum free light chain (either kappa or lambda) provided that the serum free light chain ratio is abnormal, \>0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either CT scanning or MRI
  • Subject has a Karnofsky performance status ≥60% (\>50% if due to bony involvement of myeloma (see Appendix IV)
  • Subject is able to take prophylactic anticoagulation as detailed in section 9.1 (patients intolerant to aspirin may use warfarin or low molecular weight heparin)
  • If subject is a female of childbearing potential (FCBP), ( A female of childbearing potential is a sexually mature woman who:
  • has not undergone a hysterectomy or bilateral oophorectomy; or
  • has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). She must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) 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. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with FCBP even if they have had a successful vasectomy. See Appendix III: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods
  • Subject has a life expectancy ≥ 3 months
  • Subjects must meet the following laboratory parameters:
  • Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L)
  • Hemoglobin ≥ 7 g/dL
  • Platelet count ≥ 75,000/mm3 (30 x 109/L if extensive bone marrow infiltration)
  • +3 more criteria

You may not qualify if:

  • Subject has immeasurable MM (no measurable monoclonal protein, free light chains in blood or urine, or measureable plasmacytoma on radiologic scanning)
  • Subject has a prior history of other malignancies unless disease-free for ≥ 5 years, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or localized prostate cancer with Gleason score \< 7 with stable prostate specific antigen (PSA) levels
  • Subject has had myocardial infarction within 6 months prior to enrollment, or NYHA (New York Hospital Association) Class III or IV heart failure (see Appendix VI), Ejection Fraction \< 35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Female subject who is pregnant or lactating
  • Subject has known HIV infection
  • Subject has known active hepatitis B or hepatitis C infection
  • Subject has active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program
  • Subject is unable to reliably take oral medications
  • Subject has known hypersensitivity to dexamethasone, clarithromycin, lenalidomide, or thalidomide
  • Subject has a history of thromboembolic event within the past 4 weeks prior to enrollment
  • Subject has any clinically significant medical or psychiatric disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
  • Subject has previously been treated for MM
  • Patients with symptomatic primary amiloidosis or symptomatic secondary amiloidosis (in patients with diagnosis of múltiple myeloma

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (26)

CHUAC

A Coruña, Spain

Location

Hospital Universitario Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clinic

Barcelona, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital General de Castelló

Castelló, Spain

Location

Hospital de Cabueñes

Gijón, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, Spain

Location

H. del SAS de Jerez

Jerez de la Frontera, Spain

Location

Hospital de León

León, Spain

Location

H. U. Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario de la Princesa

Madrid, Spain

Location

Hospital Costa del Sol

Marbella, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Spain

Location

Hospital Univeristario Salamanca

Salamanca, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Spain

Location

Hospital Marqués de Valdecilla

Santander, Spain

Location

Hospital Universitario de Santiago de Compostela

Santiago de Compostela, Spain

Location

Hospital Universitario Virgen de Valme

Seville, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, Spain

Location

H. Clínico de Valencia

Valencia, Spain

Location

Hospital Universitario Dr Peset

Valencia, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, Spain

Location

H. U. Txagorritxu

Vitoria-Gasteiz, Spain

Location

Related Publications (2)

  • Jelinek T, Bezdekova R, Zihala D, Sevcikova T, Anilkumar Sithara A, Pospisilova L, Sevcikova S, Polackova P, Stork M, Knechtova Z, Venglar O, Kapustova V, Popkova T, Muronova L, Chyra Z, Hrdinka M, Simicek M, Garces JJ, Puig N, Cedena MT, Jurczyszyn A, Castillo JJ, Penka M, Radocha J, Mateos MV, San-Miguel JF, Paiva B, Pour L, Rihova L, Hajek R. More Than 2% of Circulating Tumor Plasma Cells Defines Plasma Cell Leukemia-Like Multiple Myeloma. J Clin Oncol. 2023 Mar 1;41(7):1383-1392. doi: 10.1200/JCO.22.01226. Epub 2022 Oct 31.

  • Puig N, Hernandez MT, Rosinol L, Gonzalez E, de Arriba F, Oriol A, Gonzalez-Calle V, Escalante F, de la Rubia J, Gironella M, Rios R, Garcia-Sanchez R, Arguinano JM, Alegre A, Martin J, Gutierrez NC, Calasanz MJ, Martin ML, Couto MDC, Casanova M, Arnao M, Perez-Persona E, Garzon S, Gonzalez MS, Martin-Sanchez G, Ocio EM, Coleman M, Encinas C, Vale AM, Teruel AI, Cortes-Rodriguez M, Paiva B, Cedena MT, San-Miguel JF, Lahuerta JJ, Blade J, Niesvizky R, Mateos MV. Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial. Blood Cancer J. 2021 May 21;11(5):101. doi: 10.1038/s41408-021-00490-8.

Related Links

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ClarithromycinLenalidomideDexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

ErythromycinMacrolidesPolyketidesLactonesOrganic ChemicalsPhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, Fluorinated

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 12, 2015

First Posted

October 14, 2015

Study Start

September 1, 2015

Primary Completion

October 1, 2024

Study Completion

October 1, 2024

Last Updated

February 1, 2022

Record last verified: 2022-01

Locations