GEM-CLARIDEX: Ld vs BiRd (GEM-CLARIDEX)

January 17, 2022 updated by: PETHEMA Foundation

GEM-CLARIDEX: Lenalidomide and Dexamethasone (Ld) Versus Clarithromycin / Lenalidomide [Revlimid®] / Dexamethasone (BiRd) as Initial Therapy in Multiple Myeloma

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)

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

BiRd Arm

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. If a dose of clarithromycin 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.
  • 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. 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.
  • 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.

Rd Arm

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 for patients with a calculated creatinine clearance of >60 cc/min. Patients with a calculated clearance of <60 cc/min will receive 15 mgs PO daily on days 1-21 of a28 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.
  • 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.

Correlative studies: Relative dose intensity: Projected total dose per cycle of each component of assigned drug will be divided by the actual dose received and a ratio will be assessed for each cycle delivered.

MRD: Minimal residual disease testing will be performed in subjects who achieve complete response. MRD testing may be performed either by flow cytometry or polymerase chain reaction (PCR), whichever is more readily available at the study institution.

Subjects will continue their randomized treatment assignment until disease progression or unacceptable toxicity (whichever occurs first). In case toxicity precludes dosing of one agent (i.e dexamethasone, clarithromycin, lenalidomide), treatment regimen will continue with the remaining agents. Subjects unable to receive ALL the components of the assigned treatment arms will be removed from study after reasonable attempts to dose reduce and manage side effects. Subjects can also be removed from study at investigator's discretion, or if they withdraw consent. At completion or early discontinuation of treatment, subjects will be followed for 30 additional days or up to the initiation of subsequent treatment (whichever occurs first), after which they will be off the active treatment phase of the study. Long-term follow-up for disease status and survival will proceed until the subject has withdrawn consent, is lost to follow-up, or has died.

Study Type

Interventional

Enrollment (Actual)

286

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • A Coruña, Spain
        • CHUAC
      • Badalona, Spain
        • Hospital Universitario Germans Trias i Pujol
      • Barcelona, Spain
        • Hospital Clínic
      • Barcelona, Spain
        • Hospital Universitario Vall d'Hebron
      • Castelló, Spain
        • Hospital General de Castello
      • Gijon, Spain
        • Hospital de Cabueñes
      • Granada, Spain
        • Hospital Universitario Virgen de las Nieves
      • Jerez De La Frontera, Spain
        • H. del SAS de Jerez
      • León, Spain
        • Hospital de Leon
      • Madrid, Spain
        • H. U. Gregorio Marañón
      • Madrid, Spain
        • Hospital Universitario 12 De Octubre
      • Madrid, Spain
        • Hospital Universitario de La Princesa
      • Marbella, Spain
        • Hospital Costa del Sol
      • Murcia, Spain
        • Hospital General Universitario Morales Meseguer
      • Málaga, Spain
        • Hospital Universitario Virgen de la Victoria
      • Pamplona, Spain
        • Complejo Hospitalario de Navarra
      • Salamanca, Spain
        • Hospital Univeristario Salamanca
      • Santander, Spain
        • Hospital Marques de Valdecilla
      • Santiago de Compostela, Spain
        • Hospital Universitario de Santiago de Compostela
      • Sevilla, Spain
        • Hospital Universitario Virgen del Rocio
      • Sevilla, Spain
        • Hospital Universitario Virgen de Valme
      • Tenerife, Spain
        • Hospital Universitario de Canarias
      • Valencia, Spain
        • Hospital Universitario y Politecnico La Fe
      • Valencia, Spain
        • Hospital Universitario Dr Peset
      • Valencia, Spain
        • H. Clínico de Valencia
      • Vitoria, Spain
        • H. U. Txagorritxu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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:

    1. has not undergone a hysterectomy or bilateral oophorectomy; or
    2. 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)
    • Serum SGOT/AST <3.0 x upper limits of normal (ULN)ç
    • Serum SGPT/ALT <3.0 x upper limits of normal (ULN)
    • Serum total bilirubin <2.0 mg/dL (34 µmol/L)

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: BiRd

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: Clarithromycin
500mg PO twice daily on days 1-28 for a 28-day cycle
Drug: Lenalidomide
25mg PO daily on days 1-21 of a 28-day cycle for patients with a calculated creatinine clearance of >60 cc/min
Drug: Dexamethasone
40mg PO will be given on days 1, 8, 15, 22 of a 28-day cycle
ACTIVE_COMPARATOR: Rd

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: Lenalidomide
25mg PO daily on days 1-21 of a 28-day cycle for patients with a calculated creatinine clearance of >60 cc/min
Drug: Dexamethasone
40mg PO will be given on days 1, 8, 15, 22 of a 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression free survival
Time Frame: Throught the study. Approximately 4 years
Throught the study. Approximately 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PETHEMA Foundation

Collaborators

Cabyc, S.L.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 1, 2015

Primary Completion (ANTICIPATED)

October 1, 2024

Study Completion (ANTICIPATED)

October 1, 2024

Study Registration Dates

First Submitted

October 12, 2015

First Submitted That Met QC Criteria

October 13, 2015

First Posted (ESTIMATE)

October 14, 2015

Study Record Updates

Last Update Posted (ACTUAL)

February 1, 2022

Last Update Submitted That Met QC Criteria

January 17, 2022

Last Verified

January 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEM-CLARIDEX

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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