Hemotrial Un proyecto de SEHH

Ensayo clínico

Estudio de fase 3, abierto y aleatorizado, de inotuzumab ozogamicina (CMC-544) administrado en combinación con rituximab, comparado con un tratamiento definido a elección del investigador, a sujetos con linfoma no Hodgkin de células B folicular, CD22 positivo, en recidiva o refractarioAn Open-Label, Randomized, Phase 3 Study of Inotuzumab Ozogamicin (CMC-544) Administered in Combination With Rituximab Compared to a Defined Investigator’s Choice Therapy in Subjects With Relapsed or Refractory, CD22- Positive, Follicular B-Cell Non Hodgkin’s Lymphoma

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Resumen

2017-03-15 04:03:47
2007-000219-27
3129K4-3301-WW
Estudio de fase 3, abierto y aleatorizado, de inotuzumab ozogamicina (CMC-544) administrado en combinación con rituximab, comparado con un tratamiento definido a elección del investigador, a sujetos con linfoma no Hodgkin de células B folicular, CD22 positivo, en recidiva o refractarioAn Open-Label, Randomized, Phase 3 Study of Inotuzumab Ozogamicin (CMC-544) Administered in Combination With Rituximab Compared to a Defined Investigator’s Choice Therapy in Subjects With Relapsed or Refractory, CD22- Positive, Follicular B-Cell Non Hodgkin’s Lymphoma
3129K4-3301-WW

PROMOTORES DEL ENSAYO
Nombre del promotor Organización Persona de contacto País
Wyeth Research Division of Wyeth Pharmaceuticals Inc United States

Fármacos

  INFORMACIÓN DE FÁRMACOS USADOS:
  FÁRMACO 1:
Test Mitoxantrone 2mg/ml Sterile Concentrate
CP Pharmaceuticals Ltd INOTUZUMAB OZOGAMICIN
CMC-544 Intravenous infusion
Intravenous use

Detalles del Fármaco (Principio Activo):
CMC-544

Concentración del fármaco:
mg milligram(s) equal

4

Contenido del fármaco

Si
Si

No
Information no disponible en EudraCT

No
No

No
No

Information no disponible en EudraCT
No

No
No

Si
  FÁRMACO 2:
Comparator Fludara 50mg Powder for Solution for Injection or
Schering Health Care Ltd MITOXANTRONE
Concentrate for solution for infusion
Intravenous use

Detalles del Fármaco (Principio Activo):

Concentración del fármaco:
mg/ml milligram equal

2

Contenido del fármaco

Si
No

No
Information no disponible en EudraCT

No
No

No
No

Information no disponible en EudraCT
No

No
No

No
  FÁRMACO 3:
Comparator Cyclophosphamide Injection 500 mg.
Baxter Healthcare Ltd Fludarabine
Powder for solution for infusion
Intravenous use

Detalles del Fármaco (Principio Activo):

Concentración del fármaco:
mg/ml milligram equal

25

Contenido del fármaco

Si
No

No
Information no disponible en EudraCT

No
No

No
No

Information no disponible en EudraCT
No

No
No

No
  FÁRMACO 4:
Comparator Vincristine Sulphate 1mg/ml Injection
Mayne Pharma Plc CYCLOPHOSPHAMIDE
Powder for solution for injection
Intravenous use

Detalles del Fármaco (Principio Activo):

Concentración del fármaco:
mg/ml milligram equal

20

Contenido del fármaco

Si
No

No
Information no disponible en EudraCT

No
No

No
No

Information no disponible en EudraCT
No

No
No

No
  FÁRMACO 5:
Comparator MabThera
Roche Registration Limited VINCRISTINE
Solution for injection
Intravenous use

Detalles del Fármaco (Principio Activo):

Concentración del fármaco:
mg/ml milligram equal

1

Contenido del fármaco

Si
No

No
Information no disponible en EudraCT

No
No

No
No

Information no disponible en EudraCT
No

No
No

No
  FÁRMACO 6:
Test Decortin H 20 MG
Merck kGaA Rituximab / MabThera
Concentrate for solution for infusion
Intravenous use

Detalles del Fármaco (Principio Activo):

Concentración del fármaco:
mg/ml milligram equal

10

Contenido del fármaco

Information no disponible en EudraCT
Si

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
Information no disponible en EudraCT

Si
  FÁRMACO 7:
Comparator Dexamethason 4mg Galen
GALENpharma GmbH Prednisolone
Oral use

Detalles del Fármaco (Principio Activo):

Concentración del fármaco:
mg milligram(s) equal

20

Contenido del fármaco

Si
No

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
Information no disponible en EudraCT

Information no disponible en EudraCT
  FÁRMACO 8:
Comparator
DEXAMETHASONE
Oral use

Detalles del Fármaco (Principio Activo):

Concentración del fármaco:
mg milligram(s) equal

4

Contenido del fármaco

Si
No

No
Information no disponible en EudraCT

No
No

No
No

Information no disponible en EudraCT
No

No
No

Information no disponible en EudraCT
  INFORMACIÓN DE PLACEBOS USADOS:

No hay placebos asignados al ensayo

Información General

Linfomas y otros Síndromes Linfoproliferativos

Linfoma no Hodgkin de células B folicular en recidiva o refractarioRelapsed or refractory follicular B-cell Non Hodgkin's Lymphoma

To evaluate efficacy as measured by progression-free survival (PFS), with a goal of demonstrating the superiority of inotuzumab ozogamicin when administered in combination with rituximab, compared with an active comparator arm.

• To evaluate the safety and tolerability of inotuzumab ozogamicin in combination with rituximab• To evaluate the population pharmacokinetics (PK) of inotuzumab ozogamicin in combination with rituximab, and to evaluate factors affecting drug disposition• To evaluate the efficacy of inotuzumab ozogamicin in combination with rituximab using the following endpoints and analyses: • ORR (defined as CR plus unconfirmed complete response [CRu] plus partial response [PR]) • Overall survival (OS)• Health-related quality of life as assessed by the Functional Assessment of Cancer Therapy for lymphoma patients (FACT-Lym) and the European Quality of Life-5 Dimensions questionnaire (EQ-5D) • Subject self-reported fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue• QT assessment

No


1. Subjects with a diagnosis of CD20/and CD22-positive, follicular grade 1-3a lymphoma, who have received 1 or 2 prior regimens, at least 1 of which should have contained administration of rituximab (either as a single agent or in combination). Diagnoses made within 1 year of randomization do not need to be repeated. Maintenance therapy with rituximab should be considered part of the preceding induction regimen.2. Prior CD20 and /CD22-immunophenotyping of tumors to document B-cell NHL. If such prior documentation is not available, then the immunophenotype of the current disease must be documented by fine-needle aspirate or biopsy, or by circulating CD20 and/CD22-positive NHL cells from peripheral blood before randomization.3. Age 18 years or older.4. Eastern Cooperative Oncology Group (ECOG) performance status ? 2. 5. Life expectancy ? 12 weeks. 6. Absolute neutrophil count (ANC) ? 1.5 x 109/L (1500/mL) and platelets ? 75 x 109/L (75,000/mL).7. Serum creatinine ? 1.5 x the upper limit of normal (ULN) and urine protein to creatinine ratio of ? 0.2.8. Total bilirubin ?1.5 x ULN, AST and alanine aminotransferase (ALT) ? 2.5 x ULN.9. At least 1 measurable disease lesion that is ? 1.5 cm x 1.5 cm by computed tomography (CT) or magnetic resonance imaging (MRI) at the time of inclusion, in an area of no prior radiation therapy, or documented progression in an area that was previously irradiated.10. Negative serum pregnancy test performed within 1 week before administration of the first dose of test article if the subject is a woman of childbearing potential (if the subject is male, this criterion is considered to be met). A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.11. Willingness of male and female subjects who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control for the duration of the study, including up to 12 months after the last dose of test article. Sexually active males and females using oral contraceptive pills should also use barrier contraception.

1. Subjects with a prior allogeneic hematopoietic stem cell transplant (HSCT).2. Subjects with clinical evidence of transformation to a more aggressive subtype of lymphoma or gradestage 3B follicular lymphoma.3. Subjects with prior autologous transplant within 6 months before administration of the first dose of test article.4. Prior treatment with anti-CD22 antibodies or any previous radio-immuno therapy.5. Subjects whose disease is primary rituximab refractory, meaning that they did not have a CR or PR or that they experienced disease progression within 6 months after their first dose of rituximab or rituximab containing treatment regimen.6. Subjects whose disease is otherwise rituximab refractory, meaning that they did not have a CR or PR or had disease progression within 6 months after their first dose of rituximab within their second course of rituximab or rituximab-containing treatment regimen.7. Major surgery, not related to debulking surgical procedures, within 21 days before screening.8. Chemotherapy, cancer immunosuppressive therapy, radiotherapy, growth factors (except erythropoietin), or investigational agents within 28 days before administration of the first dose of test article. Subjects receiving high doses of corticosteroids must have had their doses tapered to a stable and acceptable level (i.e. physiological replacement dose) at least 28 days before administration of the first dose of test article. On dose days, subjects should not take any corticosteroids apart forfrom the premedication and corticosteroids included in the prescribed chemotherapy regimen described by the protocol, as well as any corticosteroids needed for physiological replacement.9. Prior chemotherapy with nitrosoureas or mitomycin C within 6 weeks before administration of the first dose of test article.10. Subjects who are not eligible for at least 1 of the 2 treatment options in arm 2.11. Cardiac function, as measured by left ventricular ejection fraction (LVEF), is outside of the institutional limits of normal. 12. Female subjects who are pregnant or breastfeeding (if the subject is male, this criterion is considered to be not met). 13. Central nervous system (CNS) NHL; a lumbar puncture is not required unless CNS involvement with NHL is clinically suspected.14. Subjects with known systemic vasculitides (eg, Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus).15. Known seropositivity for human immunodeficiency virus (HIV); current or chronic hepatitis B or hepatitis C infection.16. Subjects with a history of veno-occlusive disease or chronic liver disease, such as cirrhosis or chronic hepatitis due to any cause, or are suspected of alcohol abuse.17. Subjects with > grade 1 neuropathy.18. Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition, uncontrolled diabetes) or any important medical illness or abnormal laboratory finding that would, in the investigator’s judgment, increase the risk associated with the subject’s participation in the study.19. Any evidence of serious active infection (ie, requiring an intravenous [IV] antibiotic or antiviral agent).20. Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix.21. Subjects with previous malignancies are eligible provided that they have been disease free for 5 years or more. Subjects with a history of basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ, which have been successfully treated, are not excluded.

Safety:The primary endpoint of this phase 3 study is efficacy. Secondary and exploratory safety variables include evaluation of the safety and tolerability of inotuzumab ozogamicin in combination with rituximab, defined as the nature, incidence, and severity of AEs, changes in laboratory test results over time, the evaluation of the population PK of inotuzumab ozogamicin in combination with rituximab, the evaluation of factors affecting drug disposition, the assessments of impact on QT interval, and vital signs monitoring.Efficacy:The primary efficacy variable PFS is defined as the interval from the date of randomization until the earlier date of progression or death from any cause, censored at the last tumor evaluation date. Subjects with symptomatic disease progression should be documented as discontinued at the time of clinical judgment of progression, however all radiological scans should be sent to the central vendor as soon as possible. Subjects who have discontinued in this manner should continue onto disease assessment follow-up visits, if at all possible, until disease progression is declared by the independent vendor, in order to assess PFS for these subjects. Every effort should be made to obtain radiological assessments to document the objective progression even after discontinuation of treatment. If this is not possible, subjects should continue to be followed for survival.

Fase III
  DISEÑO DEL ENSAYO:

Si
Si

Si
Information no disponible en EudraCT

Information no disponible en EudraCT
Si

Information no disponible en EudraCT
Information no disponible en EudraCT
  COMPARADOR DEL ENSAYO CONTROLADO:

Si
Information no disponible en EudraCT

Information no disponible en EudraCT
No

Si

Centros participantes:

Si
Information no disponible en EudraCT
  TIEMPO ESTIMADO DURACIÓN DEL ENSAYO:

7
0
  TIEMPO ESTIMADO DURACIÓN DEL ENSAYO EN ESPAÑA:


  POBLACIÓN DE PACIENTES EN EL ESTUDIO:
  Población de pacientes: 1

Rango de edad:

0
-1

-1

Sexo:

1
1

Número planeado de pacientes a incluir:

50

Para estudios internacionales:

240
978

Investigadores

  INVESTIGADORES QUE PARTICIPAN EN EL ESTUDIO

Estado actual


 EC Finalizado



EC Finalizado