E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed or Refractory Pediatric Acute Lymphoblastic Leukemia (pALL) or Lymphoblastic Lymphoma of B-cell Origin |
Leucemia linfoblástica aguda infantil o linfoma linfoblástico B refractarios o en recidiva |
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E.1.1.1 | Medical condition in easily understood language |
Pediatric Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma |
Leucemia linfoblástica aguda infantil o linfoma linfoblástico |
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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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000845 |
E.1.2 | Term | Acute lymphoblastic leukemia |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003939 |
E.1.2 | Term | B-lymphoblastic lymphoma (Kiel Classification) |
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 |
Assess the efficacy defined as Composite Complete Response (CRc) |
Evaluar la eficacia definida como respuesta completa combinada (RCc) |
|
E.2.2 | Secondary objectives of the trial |
- Assess safety and tolerability - Assess immunogenicity and pharmacokinetics - Progression-free survival (PFS), overall survival (OS), Duration of complete response (DOCR), Duration of overall response (DOR) - Minimal residual disease negative CRc rate - Number eligible for stem cell transplant - Overall response rate (ORR) - Hematologic activity |
- Evaluar la seguridad y tolerabilidad - Evaular la ihnmunogenicidad y la farmacocinética - Supervivencia si progresión (SSP), supervivencia global (SG), duración de la respuesta completa (DRC), duración de la respuesta global (DRG) - Tasa de enfermedad residual mínima sin ERM - Número eligible para transplante de células madre - Tasa de respuesta global (TRG) - Actividad hematológica |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following criteria: 1) Between the ages of >/= 6 months and < 18 years of age 2) Written informed consent and written informed assent (if applicable) 3) Must have histologically proven B-cell ALL or B-cell lymphoblastic lymphoma 4) Measurable or evaluable disease 5) Disease status: - Subjects must have relapsed or refractory disease and received at least 1 standard chemotherapy and either 1 salvage regimen or allogeneic HSCT. - In event of relapse after prior allogeneic HSCT, subjects must be at least 3 months post-transplant, have no evidence of active graft-vs-host disease, and been off immunosuppression for at least 4 weeks - Must have resolution of the acute toxic effects to </= Grade 2 from prior chemotherapy before entry, in the opinion of the investigator 6) For non-leukemic subjects, an absolute neutrophil count (ANC) > 1000/µL, and platelet count > 50,000/mm2 are required, unless cytopenias are judged by the investigator to be due to underlying disease (ie, potentially reversible with anti-neoplastic therapy). 7) Adequate Performance status. 8) Subjects with central nervous system (CNS) status 1 or 2 are eligible only in the absence of neurologic symptoms, such as cranial nerve palsy, suggestive of CNS leukemia. 9) Sexually active subjects must agree to use an approved method of contraception or abstinence to meet eligibility criteria. |
Los sujetos deben presentar todos los criterios siguientes: 1) Edad >/= 6 meses y < 18 años en el momento de la selección. 2) Otorgamiento del consentimiento informado y de toda autorización que se exija 3) Leucemia linfoblástica aguda de células B o linfoma linfoblástico de células B con afectación medular, confirmado mediante examen histopatológico 4) Enfermedad evaluable o mensurable. 5) Estado de la enfermedad: - Recidiva o resistencia al tratamiento después de haber recibido al menos una quimioterapia convencional además de una pauta de rescate o un trasplante alogénico de progenitores hematopoyéticos. - En caso de recidiva después de un alo-TPH, deben haber transcurrido >/= 3 meses del trasplante; no debe haber signos de enfermedad del injerto contra el huésped; y el sujeto debe llevar >/= 4 semanas sin inmunosupresores. - Resolución de los efectos tóxicos agudos de la última quimioterapia a grado </= 2 antes de la inclusión, a juicio del investigador. 6) Únicamente en el caso de los sujetos que no leucémicos (o sea, con linfoma), cifra de neutrófilos (CAN) >/= 1000 /µL y cifra de plaquetas > 50.000 /mm2, a menos que el investigador considere que las citopenias obedecen al proceso neoplásico (o sea, que pueden corregirse con el tratamiento antineoplásico). 7) Estado funcional adecuado 8) Podrán participar los sujetos que presenten las categorías relativas al sistema nervioso central 1 ó 2 (SNC) únicamente si no presentan síntomas neurológicos indicativos de leucemia del SNC, como una parálisis de pares craneales: 9) Para cumplir los criterios de inclusión, los sujetos sexualmente activos deben aceptar utilizar un método anticonceptivo autorizado o evitar las relaciones sexuales |
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E.4 | Principal exclusion criteria |
Any of the following would exclude the subject from participation in the study: 1) Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results 2) Concurrent enrollment in another clinical study, unless it is a non-interventional, observational study or the subject is in the follow-up period from a previous study, or prior sponsor approval is obtained 3) Employees of the study site directly involved with the study at the site of enrollment, or immediate family members of such individuals 4) Isolated testicular or CNS ALL 5) Inadequate hepatic function 6) Inadequate renal function 7) Radiologically-detected CNS lymphoma 8) Laboratory findings consistent with Grade >/= 3 disseminated intravascular coagulation (DIC) or any Grade 2 DIC that does not correct 9) Hyperleukocytosis (WBC >/= 50,000/µL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy 10) Pregnant or breast-feeding females 11) Prior treatment with CAT-3888 (BL22), moxetumomab pasudotox, or any pseudomonas-exotoxin-containing compound 12) Prior treatment with any anticancer biologic therapy within 2 weeks prior to enrollment, including but not limited to therapeutic monoclonal antibodies or antibody-drug conjugates 13) Systemic chemotherapy </= 2 weeks (6 weeks for nitrosoureas) and radiation therapy </=3 weeks prior to starting study drug with exceptions per protocol 14) Other investigational antineoplastic agents within 30 days prior to Cycle 1, Dose of study treatment 15) Human immunodeficiency virus (HIV) positive serology 16) Seropositivity for hepatitis B (HBsAg) or hepatitis C (HCV antibody) 17) Clinically significant ophthalmologic findings during the screening 18) Uncontrolled, symptomatic, intercurrent illness that would limit study compliance 19) Presence of a second invasive malignancy 20) Any physical, social, or psychiatric condition, or any other condition which in the opinion of the investigator would prevent effective study cooperation or participation 21) Uncontrolled pulmonary infection, presence of pulmonary edema 22) Inadequate oxygen saturation 23) Serum albumin < 2 g/dL 24) Radioimmunotherapy within 2 years prior to study enrollment 25) Subject with prior history of thrombotic microangiopathy or HUS. |
El sujeto no debe presentar ninguno de los criterios siguientes para poder participar en el ensayo. -Cualquier enfermedad que a juicio del investigador dificulte la evaluación del producto en estudio o la interpretación de los resultados de seguridad o del ensayo. -Participación simultánea en otra investigación, a menos que sea de tipo observacional y no intervencionista, o bien que el sujeto se halle en una fase de seguimiento posterior al tratamiento o que se cuente con el visto bueno del promotor. -Ser trabajador del centro donde se realiza el ensayo clínico e intervenir directamente en su realización, o ser familiar directo de dichas personas. -LLA testicular o del SNC aislada. -Alteración de la función hepática: -Alteración de la function renal -Linfoma del SNC detectado mediante radiología. -Alteraciones analíticas compatibles con un cuadro de coagulación intravascular diseminada (CID) de grado >/= 3 o una CID de grado 2 que no sea corregible. -Hiperleucocitosis (>/= 50.000 leucocitos por microlitro) o progresión rápida de la enfermedad que a juicio del investigador y del promotor pongan en entredicho la capacidad de finalizar el tratamiento en estudio. -Embarazo o lactancia materna en el caso de las chicas. -Antecedentes de tratamiento con CAT-8888 (BL22), con moxetumomab pasudotox o con una molécula que contenga exotoxinas de pseudomonas. -Antecedentes de tratamiento antineoplásico con un producto biológico en las últimas 2 semanas, incluidos los anticuerpos monoclonales y los conjugados anticuerpo-fármaco. -Quimioterapia sistémica en las </= 2 semanas (6 semanas en el caso de las nitrosoureas) y radioterapia en las </=3 semanas antes de comenzar el tratamiento en estudio, con las excepciones incluidas en el protocolo -Otros antineoplásicos en fase de investigación en los 30 días anteriores a la 1.ª dosis del 1.er ciclo del fármaco en estudio, -Seropositividad del virus de la inmunodeficiencia humana (VIH). -Seropositividad de la hepatitis B (HBsAg) o la hepatitis C (anticuerpos del VHC) -Alteraciones oftalmológicas de relevancia clínica durante la selección. -Enfermedad concomitante sintomática e incontrolada que menoscabaría el cumplimiento de los requisitos del ensayo. -Presencia de una segunda neoplasia invasora; -Situación física, social, psiquiátrica o de otra índole que a juicio del investigador impida la colaboración efectiva o la participación en el ensayo. -Infección pulmonar no controlada; presencia de edema pulmonar. -Saturación de oxígeno en reposo inadecuada -Albúmina sérica < 2 g/dl. -Radioinmunoterapia en los 2 años antes de la inclusión. -Antecedentes de microangiopatía trombótica o síndrome urémico hemolítico |
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E.5 End points |
E.5.1 | Primary end point(s) |
Assess the efficacy defined as composite complete response (CRc) |
Evaluar la eficacia definida como la respuesta completa combinada (RCc) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Disease assessments will be completed prior to the first cycle and subsequent cycles |
La evaluación de la enfermedad se llevará a cabo antes del primer ciclo y de los subsecuentes |
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E.5.2 | Secondary end point(s) |
- Assess safety and tolerability - Assess immunogenicity and pharmacokinetics - PFS, OS, DOCR, DOR - Minimal residual disease negative CRc rate - Number eligible for stem cell transplant - ORR - Hematologic activity |
- Evaluar seguridad y tolerabilidad - Evaluar inmunogenicidad y farmacocinética - SSP, SG, DRC, DRG - Tasa de RCc sin enfermedad residual minima - Numero elegible para transplante de células hematopoyéticas - TRG - Actividad hematológica |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Duration of study |
Duración del estudio |
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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 | 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 | 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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Canada |
France |
Germany |
Italy |
Netherlands |
Spain |
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
|
12 months after last subject begins treatment or earlier if interim analysis performed after enrollment of the first 33 evaluable subjects shows CRc </= 21% |
12 meses después de que el último sujeto haya iniciado el tratamiento o antes si los análisis intermedios realizados tras el reclutamiento de los primeros 33 sujetos evaluables muestra una RCc </= 21% |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 9 |