E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Follicular Lymphoma |
Linfoma folicular |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025311 |
E.1.2 | Term | Lymphoma (non-Hodgkin's) |
E.1.2 | System Organ Class | 100000004864 |
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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 evaluate the efficacy of IPI-145 administered in combination with rituximab vs placebo in combination with rituximab in subjects with previously-treated CD20-positive follicular lymphoma (FL) |
? Evaluar la eficacia de IPI-145 administrado en combinación con rituximab comparado con placebo en combinación con rituximab en sujetos con linfoma folicular (LF) con reactividad para CD20 previamente tratados |
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E.2.2 | Secondary objectives of the trial |
?To evaluate the safety of IPI-145 in combination with rituximab in subjects with previously-treated CD20-positive FL ?To characterize the pharmacokinetics (PK) of IPI-145 when administered in combination with rituximab |
Evaluar la seguridad de IPI-145 en combinación con rituximab en sujetos con LF con reactividad para CD20 previamente tratados. Caracterizar la farmacocinética (FC) de IPI-145 administrado en combinación con rituximab |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There is an optional sub study for Pharmacogenomics. There is not a separate protocol, it is included in the main protocol. |
Hay un subestudio opcional farmacogenomico. No hay un protocolo separado, está incluido en el protocolo principal |
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E.3 | Principal inclusion criteria |
?Diagnosis of CD20-positive FL: oHistology grades 1, 2 or 3a o Biopsy confirmed histopathological diagnosis of FL. Biopsy specimen should be obtained ?2 years prior to randomization, unless medically contraindicated o CD20 immunophenotyping performed <2 years prior to randomization. ?First or subsequent relapse following at least one induction therapy regimen containing rituximab in combination with an anthracycline or rituximab in combination with an alkylating agent oPatients in first relapse must be chemoresistant or intolerant to chemotherapy ?No response or disease progression ? 24 months from start of last previous therapy ?At least 1 measurable disease lesion ?1.5 cm in at least one diameter by CT/CT-PET or magnetic resonance imaging (MRI) in an area of no prior radiation therapy, or in an area that was previously irradiated that has documented progression. |
-Diagnóstico de LF con reactividad para CD20 -Grados histopatológicos 1, 2 o 3a -Diagnóstico histopatológico de LF confirmado mediante biopsia.La pieza de biopsia debe obtenerse ?2 años antes de la aleatorización, salvo que esté médicamente contraindicado. Inmunofenotipificación de CD20 realizado ?2 años antes de la aleatorización 3. Primera recidiva o subsiguientes después de como mínimo un tratamiento de inducción con rituximab en combinación con una antraciclina o rituximab en combinación con un fármaco alquilante.Los pacientes que sufran una primera recidiva deberán mostrar resistencia o intolerancia a la quimioterapia. Como mínimo una lesión tumoral medible >1,5 cm en al menos un diámetro mediante TAC/TAC-TEP o resonancia magnética (RM), en un área que no haya recibido radioterapia previa, o en un área que ha recibido radioterapia previa y ha sufrido progresión documentada |
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E.4 | Principal exclusion criteria |
?Clinical evidence of other indolent forms of lymphoma (e.g., marginal zone lymphoma [MZL], small lymphocytic lymphoma [SLL]) ?Transformation to a more aggressive subtype of lymphoma or grade 3b FL ?Refractory to rituximab: defined as disease progression while receiving or within 6 months of completing either weekly rituximab induction therapy, or rituximab-based chemoimmunotherapy induction. ?Intolerance to rituximab or severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibodies ?Prior treatment with a PI3K inhibitor or BTK inhibitor |
1.Indicios clínicos de otras formas de linfoma inactivo (poco activo o de escasa malignidad) (p. ej. linfoma de zona marginal [LZM], linfoma linfocítico de células pequeñas [LLCP]) 2.Transformación a un subtipo de linfoma más agresivo o LF de grado 3b 3.Sujetos que muestran resistencia a rituximab: definida como progresión tumoral mientras reciben terapia de inducción semanal con rituximab o quimioinmunoterapia con rituximab o en el plazo de 6 meses tras completar dicha terapia 4.Intolerancia a rituximab o reacción alérgica o anafiláctica intensa a cualquier anticuerpo monoclonal murino o humanizado 5.Tratamiento anterior con un inhibidor de PI3K o un inhibidor de BTK |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS). Progression will be based on blinded independent central review. |
La progresión se basará en una revisión central independiente enmascarada. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
?Every 4 cycles for 27 cycles. ?Day 1, Cycle 28, subjects who receive IPI-145/placebo beyond 27 cycles will return to the clinic every even cycle through the end of their treatment or until disease progression. Disease response assessments will continue every 6 cycles for those subjects who continue treatment |
Cada 4 ciclos para 27 ciclos. Dia 1, ciclo 28, Los sujetos que reciban IPI-145/placebo después de los 27 ciclos volverán a la clínica cada ciclo par (ciclo 30, 32, etc.) hasta el final del tratamiento o la progresión tumoral. Las evaluaciones de la respuesta tumoral se realizarán cada 6 ciclos en sujetos que sigan recibiendo el tratamiento. |
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E.5.2 | Secondary end point(s) |
?ORR , CR, OS, DOR , TTR , EFS, PK and Safety |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
?Every 4 cycles for 27 cycles. ?Day 1, Cycle 28, subjects who receive IPI-145/placebo beyond 27 cycles will return to the clinic every even cycle through the end of their treatment or until disease progression. Disease response assessments will continue every 6 cycles for those subjects who continue treatment ?OS follow up and relevant PK and safety visits |
Cada 4 ciclos para 27 ciclos. Dia 1, ciclo 28, Los sujetos que reciban IPI-145/placebo después de los 27 ciclos volverán a la clínica cada ciclo par (ciclo 30, 32, etc.) hasta el final del tratamiento o la progresión tumoral. Las evaluaciones de la respuesta tumoral se realizarán cada 6 ciclos en sujetos que sigan recibiendo el tratamiento. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
Denmark |
France |
Germany |
Hungary |
Ireland |
Israel |
Italy |
New Zealand |
Poland |
Spain |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
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 | 9 |
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 |