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CC-4047 and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma or Amyloidosis

20 de marzo de 2018 actualizado por: Mayo Clinic

A Phase II Trial of CC-4047 Plus Dexamethasone in Patients With Relapsed of Refractory Multiple Myeloma or Amyloidosis

RATIONALE: Biological therapies, such as CC-4047, may stimulate the immune system in different ways and stop cancer cells from growing. Dexamethasone and CC-4047 may stop the growth of cancer cells by blocking blood flow to the cancer. Giving CC-4047 together with dexamethasone may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving CC-4047 together with dexamethasone works in treating patients with relapsed or refractory multiple myeloma or amyloidosis.

Descripción general del estudio

Descripción detallada

OBJECTIVES:

  • To assess the response rate and duration of remission with low-dose CC-4047 plus dexamethasone in patients with relapsed or refractory multiple myeloma or amyloidosis.
  • To assess the toxicity of CC-4047 plus dexamethasone in this patient population.
  • To assess in an expansion cohort the response rate with an increase in CC-4047 dose among patients who fail to respond adequately to the initial starting dose following the first 2 courses of treatment.
  • To assess the response rate and duration of remission with CC-4047 plus dexamethasone in patients with lenalidomide resistant or refractory multiple myeloma.
  • To assess the response rate and duration of remission with CC-4047 plus dexamethasone in patients with previously treated light chain amyloidosis.
  • To assess the response rate and duration of remission with low- and high-dose CC-4047 plus dexamethasone in patients with lenalidomide and bortezomib refractory multiple myeloma.
  • To assess the response rate and duration of remission with high-dose CC-4047 plus dexamethasone in patients with relapsed or refractory myeloma who received ≤ 3 treatment regimens.

OUTLINE: Patients are grouped according to disease status (relapsed/refractory myeloma [closed to accrual as of 8/5/2008] vs lenalidomide resistant/refractory myeloma [closed to accrual as of 4/2/2009] vs previously treated light chain amyloidosis vs lenalidomide and bortezomib resistant/refractory myeloma {low-dose/day}[closed to accrual as of 11/20/09] vs lenalidomide and bortezomib resistant/refractory myeloma (high-dose/day) vs relapsed/refractory myeloma {high-dose/day}).

Patients receive oral CC-4047 on days 1-28 and oral dexamethasone on days 1, 8, 15, and 22. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 4 weeks and then at 6 months.

Tipo de estudio

Intervencionista

Inscripción (Actual)

378

Fase

  • Fase 2

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

    • Arizona
      • Scottsdale, Arizona, Estados Unidos, 85259-5499
        • Mayo Clinic in Arizona
    • Florida
      • Jacksonville, Florida, Estados Unidos, 32224
        • Mayo Clinic in Florida
    • Minnesota
      • Rochester, Minnesota, Estados Unidos, 55905
        • Mayo Clinic

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 a 120 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

DISEASE CHARACTERISTICS:

  • Symptomatic multiple myeloma
  • Previously treated disease meeting one of the following criteria:

    • Have light-chain amyloidosis that has been treated with at least one prior regimen
    • Symptomatic (relapsed or refractory) multiple myeloma

      • Patients must have received 1-3 treatment regimens
      • Induction therapy followed by autologous stem cell transplantation and consolidation considered one regimen
  • Measurable disease, as defined by 1 of the following:

    • Serum monoclonal protein ≥ 1.0 g by protein electrophoresis
    • More than 200 mg of monoclonal protein in the urine on 24-hour electrophoresis
    • Serum immunoglobulin free light chain (FLC) > 10 mg/dL and an abnormal FLC ratio
    • Measurable soft tissue plasmacytoma, not previously irradiated
    • More than 30% plasma cells in bone marrow
  • At least 10% plasma cells as measured by bone marrow aspirate, bone marrow biopsy, or labeling index
  • No monoclonal gammopathy of undetermined significance (not applicable for patients with amyloid)
  • No smoldering myeloma (not applicable for patients with amyloid)

PATIENT CHARACTERISTICS:

  • ECOG performance status 0, 1, or 2
  • ANC ≥ 1,000/μL
  • Platelet count ≥ 75,000/μL
  • Creatinine ≤ 2.5 mg/dL
  • Not pregnant or nursing

    • Women must refrain from breastfeeding during study participation and for at least 28 days after discontinuation of study drug
  • Negative pregnancy test
  • Fertile female patients must use two reliable forms of contraception simultaneously at least 28 days before beginning, during, and at least 28 days after completion of study drug

    • The two methods of reliable contraception must include one highly effective method (i.e., intrauterine device [IUD], hormonal [birth control pills, injections, or implants], tubal ligation, or partner's vasectomy) and one additional effective (barrier) method (i.e., latex condom, diaphragm, or cervical cap)
  • Fertile male patients must use a latex condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 28 days after stopping treatment
  • Men must agree to abstain from donating semen or sperm during study participation and for 28 days after discontinuation of study drug
  • Willing to abstain from donating blood during study participation and for 28 days after discontinuation of study drug
  • No uncontrolled infection
  • No other active malignancy
  • No New York Heart Association class III or IV cardiac disease (all patients)

    • Serum troponin T > 0.10 ng/mL (amyloid patients only)
  • No known positivity for HIV or active hepatitis infection
  • No active deep vein thrombosis or pulmonary embolism that has not been therapeutically anticoagulated
  • No condition, including the presence of laboratory abnormalities, that places the patient at unacceptable risk for participating in the study or confounds the ability to interpret data from the study
  • No known hypersensitivity to thalidomide or lenalidomide including development of erythema nodosum if characterized by a desquamating rash
  • No peripheral neuropathy > grade 2

PRIOR CONCURRENT THERAPY:

  • All previous cancer therapy, including chemotherapy and investigational agents, must have been discontinued ≥ 2 weeks prior to study registration
  • No radiotherapy ≤ 14 days prior to study registration
  • No other concurrent anti-myeloma therapy
  • No concurrent radiotherapy, except for palliation of a single painful bone lesion or fracture
  • Routine concurrent bisphosphonate therapy allowed for patients with myeloma bone disease
  • Willing and able to take aspirin or alternate prophylactic anticoagulation

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: No aleatorizado
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Relapsed Myeloma (<4 Prior Regimens)

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Otros nombres:
  • CC-4047
Experimental: Lenalidomide Refractory Myeloma

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Otros nombres:
  • CC-4047
Experimental: Bortezomib/Lenalidomide Refractory/Relapsed Myeloma

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Otros nombres:
  • CC-4047
Experimental: Bortezomib/Lenalidomide Relapsed/Refractory Myeloma

Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Otros nombres:
  • CC-4047
Experimental: Relapsed Myeloma (< 4 Prior Regimens)

Pomalidomide: 4 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Otros nombres:
  • CC-4047
Experimental: Relapsed/Refractory Myeloma

Pomalidomide: 4 mg orally once daily, days 1-21 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Otros nombres:
  • CC-4047
Experimental: Relapsed Amyloidosis

Pomalidomide: 2 mg orally once daily, days 1-28 of 28 day cycle

Dexamethasone: 40 mg on days 1, 8, 15 ad 22 of 28 day cycle

40 mg/day administered through PO (with food) at Days 1, 8, 15, 22 per cycle.
2 or 4 mg/day administered through PO at days 1 - 28 or days 1-21 (see Arm description for specific dosing).
Otros nombres:
  • CC-4047

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
The Number of Confirmed Hematologic Responses (Complete, Partial, or Very Good Partial Response)
Periodo de tiempo: Duration of study (up to 3 years)

Response that was confirmed on 2 consecutive evaluations

  • Complete Response(CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and <5% plasma cells in bone marrow.
  • Very Good Partial Response(VGPR): >=90% reduction in serum M-component; Urine M-Component <100mg per 24hours; <=5% plasma cells in bone marrow.
  • Partial Response(PR): >=50% reduction in serum M-component and/or Urine M-Component >=90% reduction or <200mg per 24hours; or >=50% decrease in difference between involved and uninvolved FLC levels.
Duration of study (up to 3 years)

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Progression Free Survival (PFS)
Periodo de tiempo: Duration of study (up to 5 years)

PFS was defined as the time from registration to progression or death due to any cause. PFS was analyzed using Kaplan Meier method.

Progression was defined as any one or more of the following:

  • 25% increase in serum M-component (absolute increase >= 0.5g/dl)
  • 25% increase in urine M-component (absolute increase >= 200mg/24hour
  • 25% increase in the difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl)
  • 25% increase in bone marrow plasma cell percentage (absolute increase of >=10%)
  • Definite development of new bone lesion or soft tissue plasmacytomas
Duration of study (up to 5 years)
Duration of Response
Periodo de tiempo: Duration of study (up to 5 years)
Duration of response was calculated from the documentation (date) of first response (CR, VGPR, or PR) until the date of progression or last follow-up in the subset of patients who responded. Kaplan Meier method was used to compute this outcome.
Duration of study (up to 5 years)

Colaboradores e Investigadores

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

Patrocinador

Investigadores

  • Silla de estudio: Martha Q. Lacy, MD, Mayo Clinic

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

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 (Actual)

1 de noviembre de 2007

Finalización primaria (Actual)

1 de septiembre de 2012

Finalización del estudio (Actual)

25 de octubre de 2017

Fechas de registro del estudio

Enviado por primera vez

14 de noviembre de 2007

Primero enviado que cumplió con los criterios de control de calidad

14 de noviembre de 2007

Publicado por primera vez (Estimar)

15 de noviembre de 2007

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

18 de abril de 2018

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

20 de marzo de 2018

Última verificación

1 de marzo de 2018

Más información

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. .

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