GEM-CLARIDEX: Ld vs BiRd

Sponsor

PETHEMA Foundation (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02575144

Collaborator

Cabyc, S.L. (Industry)

286

Enrollment

Locations

Arms

109

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Clarithromycin Drug: Lenalidomide Drug: Dexamethasone	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

286 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 1, 2015

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Progression free survival [Throught the study. Approximately 4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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)
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

Contacts and Locations

Locations

	Site	City	Country
1	CHUAC	A Coruña	Spain
2	Hospital Universitario Germans Trias i Pujol	Badalona	Spain
3	Hospital Clinic	Barcelona	Spain
4	Hospital Universitario Vall d'Hebron	Barcelona	Spain
5	Hospital General de Castelló	Castelló	Spain
6	Hospital de Cabueñes	Gijon	Spain
7	Hospital Universitario Virgen de las Nieves	Granada	Spain
8	H. del SAS de Jerez	Jerez De La Frontera	Spain
9	Hospital de León	León	Spain
10	H. U. Gregorio Marañón	Madrid	Spain
11	Hospital Universitario 12 de Octubre	Madrid	Spain
12	Hospital Universitario de la Princesa	Madrid	Spain
13	Hospital Costa del Sol	Marbella	Spain
14	Hospital General Universitario Morales Meseguer	Murcia	Spain
15	Hospital Universitario Virgen de la Victoria	Málaga	Spain
16	Complejo Hospitalario de Navarra	Pamplona	Spain
17	Hospital Univeristario Salamanca	Salamanca	Spain
18	Hospital Marqués de Valdecilla	Santander	Spain
19	Hospital Universitario de Santiago de Compostela	Santiago de Compostela	Spain
20	Hospital Universitario Virgen de Valme	Sevilla	Spain
21	Hospital Universitario Virgen del Rocío	Sevilla	Spain
22	Hospital Universitario de Canarias	Tenerife	Spain
23	H. Clínico de Valencia	Valencia	Spain
24	Hospital Universitario Dr Peset	Valencia	Spain
25	Hospital Universitario y Politécnico La Fe	Valencia	Spain
26	H. U. Txagorritxu	Vitoria	Spain