| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| PATIENTS WITH MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA (MALT) FOR WHICH THE STANDARD TREATMENTS WITH RADIOTHERAPY, CHEMOTHERAPY AND /OR IMMUNOTHERAPY SHOW LACK OF EFFICACY |
| Pacientes con linfoma tipo MALT (asociado a las mucosas) donde los tratamientos estandar con radioterapia, quimioterapia y/o inmunoterapia no muestran eficacia |
|
| E.1.1.1 | Medical condition in easily understood language |
| PTS WITH STRONG FORM OF CANCER. IT AFFECTS CELLS AND TISSUES RESPONSIBLE FOR DEFENDING THE BODY AGAINST EXTERNAL AGENTS/ DISEASE. THIS TUMOR GROWS AT EXPENSE OF LYMPHOID TISSUE IN THE MUCOUS MEMBRANES |
| Pacientes con cancer agresivo. Afecta a células y tejidos responsables de defender al organismo de agentes externos y enfermedades. El tumor crece en tejido linfoide de membranas mucosas |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the overall response rate (complete and partial responses) of the combination treatment of clarithromycin and lenalidomide (Revlimid) in patients with MALT lymphoma, refractory or relapsing after radiotherapy and/or chemotherapy and/or immunotherapy. |
| Evaluar la tasa de respuesta global (respuesta parcial y completa) de la combinación de claritromicina y lenalidomida (Revlimid) en pacientes con linfoma MALT, refractario o en recaída después de radioterapia y/o quimioterapia y/o inmunoterapia |
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| E.2.2 | Secondary objectives of the trial |
1. To evaluate the safety profile of the clarithromycin + lenalidomide combination, including any late adverse reactions
2. To assess the progression-free survival after clarithromycin + lenalidomide therapy
3. To assess the time to progression after clarithromycin + lenalidomide therapy
4. To assess the overall survival after clarithromycin+lenalidomide therapy |
1. Evaluar el perfil de seguridad de la combinación de claritromicina y lenalidomida, incluyendo efectos adversos tardíos
2. Evaluar la supervivencia libre de progresión después de tratamiento con la combinación de claritromicina y lenalidomida
3. Evaluar el tiempo hasta progresión después de tratamiento con la combinación de claritromicina y lenalidomida
4. Evaluar la supervivencia global después de tratamiento con claritromicina y lenalidomida |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Histologically verified diagnosis of MALT lymphoma arising at any extranodal site
2) Disease refractory to or in first or greater relapse after prior radiotherapy and/or chemotherapy and/or immunotherapy
3)Measurable or non-measurable lesions where the response is nevertheless evaluable by non-imaging means (e.g., gastric or bone marrow infiltrations)
4) Ann Arbor Stage I-IV
5) ECOG performance status of 0, 1 or 2
6) Age ≥ 18 years
7) Life expectancy of at least 3 months
8) Adequate haematological status: ANC (absolute neutrophil count [segmented + bands]) ≥1.0 x 109/L, platelet count ≥ 75 x 109/L , haemoglobin ≥8 g/dL.
9) Adequate cardiac, renal and liver function tests (LVEF > 40%, serum creatinine < 2.5 mg/dl, ALAT or ASAT < 2.5 x upper limit of normal range, alkaline phosphatase < 2.5 x upper limit of normal range, serum bilirubin < 2.0 mg/dl)
10) Patient must be willing and able to comply with the protocol for the entire study duration
11) Female patients of childbearing potential must agree to use, and be able to comply with, effective contraception and agree to have medically supervised pregnancy tests prior to starting the study treatment and during therapy
12) Male patients must agree to always use a condom during any sexual contact with females of reproductive potential and agree to not donate sperm while taking lenalidomide
13) Patient must agree to abstain from donating blood while taking study drug therapy
14) Patient must agree not to share study medication with another person and to return all unused study drug to the investigator
15) Patient must be willing and able to comply with the protocol
16) Patient must be capable of understanding the purpose of the study and have given written informed consent |
1. Diagnostico verificado histologicamente de linfoma MALT en cualquier sede extranodal
2. Enferemdad refractaria o en primera o ulterior recaida tras radioterapia y/o quimioterapia y/o inmunoterpia
3. Lesiones medibles o no medibles donde la respuesta es de todas formas evaluable por medios distintos de la imagen (por ejemplo, infiltración gastrica o de la médula ósea)
4. Estadio Ann Arbor I-IV
5. ECOG performance status de 0,1 o 2
6. dad ≥ 18 años
7.Esperanza de vida de al menos 3 meses
8.Estado hematológico adecuado: ANC (recuento absoluto de neutrófilos [segmentado + bandas]) ≥1,0 x 109 / L, recuento de plaquetas ≥ 75 x 109 / L, hemoglobina ≥8 g / dL.
9.Pruebas de función cardíaca, renal y hepática adecuadas (FEVI> 40%, creatinina sérica <2,5 mg / dl, ALAT o ASAT <2,5 x límite superior del rango normal, fosfatasa alcalina <2,5 x límite superior del rango normal, bilirrubina sérica < 2,0 mg / dl)
10.El paciente debe estar dispuesto y capaz de cumplir con el protocolo durante toda la duración del estudio
11.Las mujeres con potencial reproductivo deben acordar el uso y poder cumplir con la anticoncepción efectiva y acordar la realización de pruebas de embarazo médicamente supervisadas antes de comenzar el tratamiento del estudio y durante la terapia
12.Los pacientes varones deben aceptar usar siempre un condón durante cualquier contacto sexual con las mujeres de potencial reproductivo y aceptar no donar esperma mientras están tomando lenalidomida
13.El paciente debe aceptar abstenerse de donar sangre mientras toma el medicamento del estudio
14.El paciente debe acordar no compartir la medicación del estudio con otra persona y devolver todos los medicamentos del estudio no utilizados al investigador
15.El paciente debe estar dispuesto y capaz de cumplir con el protocolo
16.El paciente debe ser capaz de entender el propósito del estudio y haber dado su consentimiento informado por escrito
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| E.4 | Principal exclusion criteria |
1) Lymphoma histology other than MALT lymphoma or MALT lymphoma with a diffuse large cell lymphoma (“high grade lymphoma”) - component
2) Use of any investigational agent within 28 days prior to initiation of treatment
3) History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix within the last 5 years unless in complete remission since at least 3 years
4) Dependency on red blood cell and/or platelet transfusions
5) HBsAg positivity
6) Evidence of central nervous system involvement
7) A history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs
8) Severe peripheral polyneuropathy
9) Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months and/or long QT-syndrome
10) HIV seropositivity
11) Presence of active opportunistic infections
12) Pregnancy or lactation
13) Uncontrolled diabetes mellitus
14) Pre-existing thromboembolic conditions at study entry
15) Known hypersensitivity to thalidomide or lenalidomide or macrolide antibiotics
16) Presence of any contraindication reported on the Summary of Product Characteristics (SmPC) of Clarithromycin
17) Hypersensitivity to any active principle and/or any excipient according to the contraindications reported in the SmPC of clarithromycin and in the Investigator’s Brochure (IB) of lenalidomide |
1) Linfoma histológico distinto al linfoma MALT o linfoma MALT con linfoma difuso de células grandes ("linfoma de alto grado")
2) El uso de cualquier farmaco experimental los 28 días previos al inicio del tratamiento
3) Historial de neoplasias malignas distintas del carcinoma de células escamosas, carcinoma basocelular de la piel o carcinoma in situ del cuello uterino en los últimos 5 años, salvo en remisión completa desde al menos 3 años
4) Dependencia de transfusiones de glóbulos rojos y / o plaquetas
5) HBsAg positivo
6) Afectación del sistema nervioso central
7) Un historial de epilepsia no controlada, trastornos del sistema nervioso central o discapacidad psiquiátrica juzgado por el investigador clínicamente significativo y que afecta negativamente al cumplimiento de los fármacos del estudio.
8) Polineuropatía periférica grave
9) Enfermedad cardíaca clínicamente significativa (por ejemplo, insuficiencia cardíaca congestiva, enfermedad arterial coronaria sintomática y arritmias cardiacas no bien controladas con medicación) o infarto de miocardio en los últimos 6 meses y / o síndrome de QT largo
10) Seropositividad al VIH
11) Presencia de infecciones oportunistas activas
12) Embarazo o lactancia
13) Diabetes mellitus incontrolada
14) Condiciones tromboembólicas preexistentes en la entrada del estudio
15) Hipersensibilidad conocida a talidomida o lenalidomida o antibióticos macrólidos
16) Presencia de cualquier contraindicación reportada en el Resumen de Características del Producto (SMPC) de Claritromicina
17) Hipersensibilidad a cualquier principio activo y / o cualquier excipiente de acuerdo con las contraindicaciones reportadas en el SmPC de claritromicina y en el Folleto del investigador (IB) de lenalidomida |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Tumor response assessed according to the international Revised Response Criteria for Malignant Lymphoma (Cheson et al) and the GELA (Group d'Etude des Lymphomes de l'Adulte) histological scoring system for post-treatment biopsies of patients with gastric MALT lymphoma. The overall response rate will be represented by the total number of complete and partial responses. |
La respuesta tumoral se evaluó de acuerdo con el Criterio de Respuesta Revisado Internacional para el Linfoma Maligno (Cheson et al) y el sistema de puntuación histológica GELA (GELA) para biopsias postratamiento de pacientes con linfoma MALT gástrico. La tasa de respuesta global estará representada por el número total de respuestas completas y parciales.
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| For the whole duration of the study |
| Para la entera duración del estudio |
|
| E.5.2 | Secondary end point(s) |
1) Adverse events incidence, severity and relationship to study treatment
2) Time from first investigational medicinal product administration to assessment of disease progression or death due to any cause
3) Time from first investigational medicinal product administration to assessment of disease progression or death due to progression
4) Time from first IMP administration to patient’s Death |
1) Incidencia de eventos adversos, gravedad y relación con el tratamiento del estudio
2) Tiempo transcurrido desde la primera administración del medicamento en investigación hasta la evaluación de la progresión de la enfermedad o la muerte por cualquier causa
3) Tiempo transcurrido desde la primera administración del medicamento en fase experimental hasta la evaluación de la progresión de la enfermedad o la muerte por progresión
4) Tiempo desde la primera administración IMP hasta la muerte del paciente |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| For the whole duration of the study |
| Para la entera duración del estudio |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Yes |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 14 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Austria |
| Italy |
| Spain |
| Switzerland |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| LVLS AFTER 10 YEARS OF FOLLOW-UP |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 13 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 13 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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