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Pilot Lenalidomide in Adult Diamond-Blackfan Anemia Patients w/ RBC Transfusion-Dependent Anemia

27 de junio de 2017 actualizado por: Jason Robert Gotlib

A Pilot Study of Lenalidomide in Adult Diamond-Blackfan Anemia Patients With Red Blood Cell Transfusion-Dependent Anemia

This is a single-center, single arm, open-label study of oral lenalidomide monotherapy administered to red blood cell (RBC) transfusion dependent adult subjects with Diamond-Blackfan Anemia (DBA).

Primary Objective: To evaluate the erythroid response rate as measured by rate of red blood cell transfusion independence [MDS International Working Group (IWG) 2000 Criteria will be applied].

Secondary Objective: 1)To evaluate the tolerability and safety profile of lenalidomide in patients with DBA and other inherited marrow failure syndromes 2) To correlate response to lenalidomide with biologic surrogates of DBA including ribosomal protein mutation status, ex vivo erythroid colony growth, and microarray gene expression

Descripción general del estudio

Descripción detallada

This pilot study will utilize an intra-patient dose escalation design. Cycles are 28 days in length. Subjects will receive lenalidomide 2.5 mg weekly during days 1 to 21 of cycle 1 (dose level 1). If patients do not experience any grade > 3 hematologic or non-hematologic toxicity, the dose will be increased to 2.5 mg twice weekly on days 1 to 21 of cycle 2 (dose level 2). If patients do not experience any grade > 3 hematologic or non-hematologic toxicity, the dose will be increased to 5 mg twice weekly on days 1 to 21 of cycle 3 (dose level 3). If patients do not experience any grade >3 hematologic or non-hematologic toxicity, the dose will be increased to 5 mg thrice weekly on days 1 to 21 of cycle 4 (dose level 4). Patients who experience grade >3 hematologic or non-hematologic toxicity at dose level 1 will be discontinued from study. Patients who experience grade > 3 hematologic or non-hematologic toxicity at dose level 2, 3, or 4 will have the lenalidomide held and dose reduced according to protocol dose interruption/modification algorithms (section 5.5.3). If at least a minor erythroid response is not achieved at the end of 8 cycles of treatment, patients will be discontinued from study. If a minor or major erythroid response is achieved after completion of 8 cycles of treatment, patients can continue study drug on a maintenance phase until loss of erythroid response (return to baseline hemoglobin or transfusion requirement) or unacceptable toxicity.

Tipo de estudio

Intervencionista

Inscripción (Actual)

2

Fase

  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

    • California
      • Stanford, California, Estados Unidos, 94305
        • Stanford University School of Medicine

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

INCLUSION CRITERIA

  • Understand and voluntarily sign an informed consent form
  • Diagnosis of DBA
  • Age ≥ 18 years at the time of signing the informed consent form.
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Red blood cell transfusion-dependent with a requirement of at least one unit of RBCs per month for the 2 months prior to study enrollment (eg, 2 units/8 weeks)
  • If applicable, ongoing therapy with a stable or decreasing dose of prednisone ≤ 60 mg/d or corticosteroid equivalent, for which there has been no treatment-related improvement in RBC transfusion requirements for at least 2 months prior to study entry
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry.
  • Laboratory test results within these ranges:

    • Absolute neutrophil count (ANC) ≥ 1500/uL
    • Platelet (Plt) count ≥ 100,000/uL
    • Serum creatinine ≤ 2.0 mg/dL
    • Direct bilirubin ≤ 1.5 mg/dL
    • Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
    • Alanine aminotransferase (ALT) ≤ 2.5 x ULN
    • Disease-free of prior malignancies for ≥ 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ" of the cervix or breast
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of ≥ 50 milli-International Units (MIU)/mL within 10 to 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control, one highly effective method and one additional effective method at the same time, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy
  • Able to take aspirin (81 to 325 mg) daily as prophylactic anticoagulation (patients intolerant to aspirin may use warfarin or low molecular weight heparin)

EXCLUSION CRITERIA

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide)
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Use of any other experimental drug or therapy (excluding steroids) specifically used for DBA within 28 days of baseline including metoclopramide, leucine, danazol, or other hormonal therapy
  • Clinically significant anemia due to factors such as iron, B12, folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding.
  • Known hypersensitivity to thalidomide
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Any prior use of lenalidomide
  • Concurrent use of other anti-cancer agents or treatments
  • Known positive for HIV or infectious hepatitis, type A, B or C

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Lenalidomide
Subjects will initially receive lenalidomide 2.5 mg, and may escalate up to 2.5 mg/wk up to 5 mg 3x/wk, depending toxicity and response.
2.5 mg/wk up to 5 mg 3x/wk
Otros nombres:
  • CC-5013
  • Revlimid

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Red Blood Cell (RBC) Transfusion Independence
Periodo de tiempo: 6 months
Red blood cell (RBC) transfusion independence is reported as the number of subjects who achieve a continuous absence of the intravenous infusion of any RBC transfusion during any consecutive "rolling" 56 days during the treatment period.
6 months

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Red Blood Cell (RBC) Transfusions
Periodo de tiempo: 6 months
The effect on red blood cell (RBC) transfusions was assessed as the number of participants that achieved a greater than 50% decrease in RBC transfusion requirements.
6 months
Hemoglobin Concentration
Periodo de tiempo: 6 months
The effect on hemoglobin concentration was assessed as the change from baseline, measured in g/dL.
6 months
Neutrophil Response
Periodo de tiempo: 6 months
The effect on neutrophil levels was assessed as the change in neutrophil count from baseline.
6 months
Platelet Response
Periodo de tiempo: 6 months
The effect on platelet levels as assessed as the change in platelet count from baseline.
6 months
Duration of Response
Periodo de tiempo: 6 months
The response duration was measured from the last of the consecutive 56 days during which the subject was free of red blood cells (RBC) transfusions to the date of the first RBC transfusion after the 56-day RBC-transfusion-free period.
6 months
Toxicity
Periodo de tiempo: 6 months
Toxicity was assessed as the number of adverse events related to lenalidomide.
6 months

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Colaboradores

Investigadores

  • Investigador principal: Jason Robert Gotlib, Stanford University

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de noviembre de 2009

Finalización primaria (Actual)

1 de octubre de 2012

Finalización del estudio (Actual)

1 de diciembre de 2012

Fechas de registro del estudio

Enviado por primera vez

15 de diciembre de 2009

Primero enviado que cumplió con los criterios de control de calidad

15 de diciembre de 2009

Publicado por primera vez (Estimar)

17 de diciembre de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

2 de agosto de 2017

Última actualización enviada que cumplió con los criterios de control de calidad

27 de junio de 2017

Última verificación

1 de junio de 2017

Más información

Términos relacionados con este estudio

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

NO

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

Ensayos clínicos sobre Lenalidomide

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