E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The hematologic disease known as Waldenstrom’s Macroglobulinemia (WM). WM is a type of Lymphoplasmacytic lymphoma (LPL), a rare and chronic form of B-cell non-Hodgkin lymphoma (NHL), characterized by small B lymphocytes, plasmacytoid lymphocytes, and plasma cells typically involving the bone marrow, lymph nodes, and spleen. |
La enfermedad hematológica conocida como macroglobulinemia de Waldenstrom (WM). La WM es un tipo de linfoma linfoplasmocítico (LPL), una forma rara y crónica de linfoma no Hodgkin de células B (LNH), que se caracteriza por linfocitos B pequeños, linfocitos plasmocitoides y células plasmáticas que suelen afectar la médula ósea, los ganglios linfáticos y bazo. |
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E.1.1.1 | Medical condition in easily understood language |
Waldenstrom’s Macroglobulinemia is a specific type of cancer that form in certain blood cells known as B-cells. B-cells are part of the immune system. |
La macroglobulinemia de Waldenstrom es un tipo específico de cáncer que se forma en ciertas células sanguíneas conocidas como células B. Las células B forman parte del sistema inmunológico. |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054695 |
E.1.2 | Term | Waldenstrom's macroglobulinemia |
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 |
The primary objective of the study is to determine the major response rate (MRR) of CLR 131 in patients with WM who have received at least two prior lines of therapy. |
El objetivo principal del estudio es determinar la tasa de respuesta importante (TRI) de CLR 131 en pacientes con MW que han recibido al menos dos líneas de tratamiento previas. |
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E.2.2 | Secondary objectives of the trial |
• To determine the overall response rate (ORR), treatment free survival (TFS), duration of response (DOR), and clinical benefit rate (CBR) in the population under study • To further describe the safety and tolerability profile of CLR 131 in the population under study, and in sub-populations |
• Determinar la tasa de respuesta global (TRG), la supervivencia sin tratamiento (SST), la duración de la respuesta (DR) y la tasa de beneficio clínico (TBC) en la población estudiada. • Describir mejor el perfil de seguridad y tolerabilidad de CLR 131 en la población estudiada y en subpoblaciones. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histologically or cytologically confirmed WM. Patients with a diagnosis of LPL may be enrolled with prior Sponsor approval. 2. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2. 3. Patient is 18 years of age or older. 4. Life expectancy of at least 6 months. 5. Received at least two prior lines of therapy for WM. |
1. MW confirmada histológica o citológicamente. Los pacientes con diagnóstico de LLP podrán participar con la aprobación previa del promotor. 2. El paciente tiene un estado funcional (EF) del Eastern Cooperative Oncology Group (ECOG) de 0 a 2. 3. Tener 18 años o más. 4. Esperanza de vida de al menos 6 meses. 5. El paciente ha recibido al menos dos líneas de tratamiento previas para la MW |
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E.4 | Principal exclusion criteria |
1. Ongoing Grade 2 or greater toxicities due to previous therapies, excluding alopecia 2. Prior external-beam RT resulting in greater than 20% of total bone marrow receiving greater than 20 Gy. 3. Prior total body or hemi-body irradiation. Patients who have received prior low-dose total body or hemi-body irradiation may be allowed on a case-by-case basis after discussion with Sponsor (considerations may include factors such as time since irradiation, total lifetime accumulated dose, etc.). 4. Patients with second malignancies in addition to WM, if the second malignancy has required therapy in the last 2 years or is not in remission; exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy. 5. Anti-cancer therapy within two weeks of initial CLR 131 infusion. 6. Major surgery within 6 weeks of enrollment. 7. History of hypersensitivity to thyroid protection medication (e.g., potassium iodide, Lugol’s solution, etc.). 8. Known history of human immunodeficiency virus, hepatitis C, or hepatitis B infection. 9. Presence of active infection within 72 hours prior to dosing; patients with ongoing use of prophylactic antibiotics, antifungals, or antivirals are eligible as long as there is no evidence of active infection and the antibiotics, antifungals, or antivirals are not included on the list of prohibited medications. 10. Pregnancy or breast-feeding. |
1. Toxicidad de grado 2 o superior en curso debida a tratamientos previos, excluida la alopecia. 2. Radioterapia (RT) de haz externo previa que haga que más del 20 % de la médula ósea total reciba más de 20 Gy. 3. Irradiación corporal total o hemicorporal previa. Los pacientes que hayan recibido dosis bajas previas de irradiación corporal total o hemicorporal podrán participar en función de cada caso previa consulta con el promotor (las consideraciones pueden incluir factores como el tiempo transcurrido desde la irradiación, la dosis acumulada total durante toda la vida, etc.). 4. Pacientes con segundas neoplasias malignas además de MW, si la segunda neoplasia maligna ha precisado tratamiento en los 2 últimos años o no está en remisión; las excepciones a este criterio son el carcinoma basocelular o epidermoide no metastásico tratado con éxito o el cáncer de próstata que no requiere tratamiento. 5. Tratamiento antineoplásico en las dos semanas previas a la infusión inicial de CLR 131. 6. Intervención de cirugía mayor en las 6 semanas previas a la inclusión. 7. Antecedentes de hipersensibilidad a medicamentos de protección tiroidea (p. ej., yoduro potásico, solución de Lugol, etc.). 8. Antecedentes conocidos de infección por el virus de la inmunodeficiencia humana, hepatitis C o hepatitis B. 9. Presencia de infección activa en las 72 horas previas a la administración; los pacientes que estén recibiendo antibióticos, antifúngicos o antivíricos profilácticos podrán participar siempre que no haya indicios de infección activa y que los antibióticos, antifúngicos o antivíricos no estén incluidos en la lista de medicamentos prohibidos. 10. Embarazo o lactancia. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the MRR, which is defined as the proportion of patients following the infusion of CLR 131 with complete response (CR), very good partial response (VGPR), or partial response (PR) determined from criteria modified from the VIth Waldenstrom’s Macroglobulinemia Criteria for Response Assessment up to 12 months post first CLR 131 infusion in WM patients who have received at least two prior lines of therapy. |
El criterio de valoración principal es la TRI, que se define como la proporción de pacientes tras la infusión de CLR 131 con respuesta completa (RC), respuesta parcial muy buena (RPMB) o respuesta parcial (RP) determinada a partir de los criterios modificados de los VI Criterios de macroglobulinemia de Waldenström para la evaluación de la respuesta (véase el apéndice G) hasta 12 meses después de la primera infusión de CLR 131 en pacientes con MW que han recibido al menos dos líneas de terapia anteriores. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 8, 15, 22, 29, 36, 43, 50, 57 Month 6 post first CLR 131 infusion year 1 post first CLR 131 infusion |
Día 8, 15, 22, 29, 36, 43, 50, 57 Mes 6 después de la primera infusión de CLR 131 año 1 después de la primera infusión de CLR 131 |
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E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints include ORR, TFS, DOR, CBR, and safety. Overall response rate is defined as the proportion of patients with a minor response (MR), PR, VGPR, or CR determined from criteria modified from the VIth Waldenstrom’s Macroglobulinemia Criteria for Response Assessment. Treatment free survival is defined as the time from last CLR 131 dose to time to initiation of subsequent therapy or death. Duration of response is defined as the time from the first documentation of response (including CR, VGPR, PR) to progressive disease (PD) or death. Clinical benefit rate is defined as the proportion of patients with CR, VGPR, PR, MR, and SD determined from criteria modified from the VIth Waldenstrom’s Macroglobulinemia Criteria for Response Assessment. |
Los criterios de valoración secundarios de la eficacia serán la TRG, la SST, la DR, la TBC y la seguridad. La tasa de respuesta global se define como la proporción de pacientes con una respuesta menor (RM), RP, RPMB o RC determinada a partir de los criterios modificados de los VI Criterios de macroglobulinemia de Waldenström para la evaluación de la respuesta. La supervivencia sin tratamiento se define como el tiempo transcurrido desde la última dosis de CLR 131 hasta el inicio del tratamiento posterior o la muerte. La duración de la respuesta se define como el tiempo transcurrido desde la primera documentación de respuesta (incluidas RC, RPMB, RP) hasta la progresión de la enfermedad (PE) o la muerte. La tasa de beneficio clínico se define como la proporción de pacientes con RC, RPMB, RP, RM y EE determinada a partir de los criterios modificados de los VI Criterios de macroglobulinemia de Waldenström para la evaluación de la respuesta. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 1, 8, 15, 22, 29, 36, 43, 50 and 57 Month 6 post first CLR 131 infusion year 1 post first CLR 131 infusion AE/SAE profile is evaluated at all visits |
Día 1, 8, 15, 22, 29, 36, 43, 50 y 57 Mes 6 después de la primera infusión de CLR 131 Año 1 después de la primera infusión de CLR 131 El perfil AE / SAE se evalúa en todas las visitas |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.3 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 |
Brazil |
Israel |
Turkey |
United States |
France |
Portugal |
United Kingdom |
Spain |
Czechia |
Greece |
Italy |
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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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Patients will be assessed for approximately 3 years post initial CLR 131 dosing. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |