Hemotrial Un proyecto de SEHH

Ensayo clínico

Estudio de Fase Ib, multicéntrico, de determinación de dosis, con un fase II doble ciego, controlado con placebo, aleatorizado, adaptativo, que utiliza varias dosis IV repetidas de BHQ880 en combinación con ácido zoledrónico, en pacientes con mieloma refractario o en recaída y con complicaciones esqueléticas previas.

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Resumen

2017-03-15 04:07:25
2008-000411-15
CBHQ880A2102
Estudio de Fase Ib, multicéntrico, de determinación de dosis, con un fase II doble ciego, controlado con placebo, aleatorizado, adaptativo, que utiliza varias dosis IV repetidas de BHQ880 en combinación con ácido zoledrónico, en pacientes con mieloma refractario o en recaída y con complicaciones esqueléticas previas.
CBHQ880A2102

PROMOTORES DEL ENSAYO
Nombre del promotor Organización Persona de contacto País
Novartis Farmacéutica, S.A Spain

Fármacos

  INFORMACIÓN DE FÁRMACOS USADOS:
  FÁRMACO 1:
Test ZOMETA 4 mg/5 ml concentrado para solución
NOVARTIS EUROPHARM LTD. BHQ880
BHQ880 Powder for solution for infusion
Intravenous use

Detalles del Fármaco (Principio Activo):
BHQ880 ACIDO ZOLEDRONI

Concentración del fármaco:
mg/ml milligram equal

100

Contenido del fármaco

No
Si

No
Information no disponible en EudraCT

No
No

No
No

Information no disponible en EudraCT
No

No
No

Si
  FÁRMACO 2:
Test
Powder and solvent for solution for infusion
Intravenous use

Detalles del Fármaco (Principio Activo):

Concentración del fármaco:
mg/ml milligram 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

No
  INFORMACIÓN DE PLACEBOS USADOS:
  PLACEBO 1:

Si
Solution for infusion

Intravenous use

Información General

Mielomas

Mieloma Múltiple refractario o en recaída.

Escalation phase (Phase I):1. To determine the maximum-tolerated dose (MTD) and to characterize dose limitingtoxicity (DLT) of escalating doses of BHQ880 (up to a maximum dose of 20 mg/kg) incombination with standard anti-myeloma therapy and zoledronic acid.Expansion phase (Phase II):1. To determine one or more doses of BHQ880 for further development based on dose efficacy modeling, where efficacy is relative to placebo in terms of time to first SRE from randomization and change in bone markers for bone resorption and formation in combination with zoledronic acid plus standard anti-myeloma therapy

In relapsed or refractory multiple myeloma patients in combination with zoledronic acid plus standard anti-myeloma therapy, to:1. characterize acute and chronic safety and tolerability of various doses of BHQ880 2. characterize single-dose and repeated-dose PK profiles of iv administrated BHQ8806. determine the PD effects of BHQ880 by measuring biochemical markers of bone formation, resorption, and metabolism in serum and urine7. assess the effect of BHQ880 on the Ca2+ and P+ metabolism8. monitor preliminary evidence of anti-tumor activity of BHQ880 9. investigate the effect of BHQ880 in combination on the radiographic size and number of lytic bone lesions as measured by bone survey 3. To assess the potential immunogenicity of iv infused BHQ8804. To characterize the binding kinetics of DKK1/BHQ880 complex in serum5. To characterize changes in serum DKK1 levels during treatment

Si

Estudio de Biomarcadores Exploratorios y Farmacogenética. Objetivos: detectar cualquier cambio en el metabolismo óseo pre y post tratamiento para identificar posibles dosis de BHQ880 para el desarrollo posterior en esta población. Se evaluará la acti

1. Relapsed or refractory multiple myeloma patients requiring treatment with a nonbortezomib-containing regimen (prior treatment with bortezomib is acceptable)2. The diagnosis of symptomatic multiple myeloma as defined by the following criteria(International Myeloma Working Group):? M-protein in serum or urine? Clonal bone marrow plasma cells or plasmacytoma? Presence of related organ or tissue impairment (ROTI)3. Patients with multiple myeloma who do not have measurable serum M-protein ormeasurable urine M-protein must have measurable increased concentrations of free lightchains (using FreeLite)4. At least one prior SRE defined as one of the following:? Pathologic fracture? Spinal cord compression? Requirement for either radiation or surgery to bone due to:- Pain- Prevention of imminent fracture- Stabilization of a fracture5. Stable renal function defined as two serum creatinine determinations of < 2.5 mg/dl orcalculated (Cockroft-Gault formula) creatinine clearance (CrCl) < 60 mL/min.? Cockcroft-Gault formula (Cockcroft and Gault 1976):? CrCl = [140-age (years)] x weight (kg) (x 0.85 for female patients)[72 x serum creatinine (mg/dL)]6. Current or planned treatment with zoledronic acid7. No symptoms of hyperviscosity, amyloidosis or recurrent infection8. Corrected serum calcium < 12 mg/dl or ionized calcium < 6.5 mg/dL within 14 days priorto registration9. Life expectancy of at least 12 months.10. Ambulatory patients aged 18 years or older11. ECOG performance status ? 212. Absolute neutrophil count ? 1500/mm313. Platelet count ? 75,000/mm314. Hemoglobin (Hgb) ? 9 g/dl (prior RBC transfusion, recombinant epoetin alfa, ordarbepoetin alfa allowed)15. Electrolyte levels ? LLN (i.e., potassium, magnesium, phosphorus) correction withsupplements allowed16. AST and ALT ? 2.5 x ULN17. Serum bilirubin ? 1.5 x ULN18. Patients must sign the informed consent form and be willing and able to comply with thestudy protocol

1. Known concomitant disease(s) known to influence Ca2+ metabolism includinghyperparathyroidism, hyperthyroidism and/or Paget?s disease of bone.2. Current active dental problems including? Ongoing infection of the teeth or jawbone ? Current exposed bone in the mouth? Dental or fixture trauma? Current or previous osteonecrosis of the jaw? Slow healing after dental procedures? Recent (within 6 weeks) or planned dental or jaw surgery during the study 3. Prior radiation therapy to treat diseases of the mouth4. Patients who are allergic to/ intolerant of bisphosphonate therapy5. Acute or chronic liver disease6. Patients with any peripheral neuropathy ? CTCAE grade 27. Other concurrent severe and/or uncontrolled concomitant medical conditions that couldcause unacceptable safety risks or compromise compliance with the protocol8. Angina pectoris ? 3 months prior to starting study drug9. Acute myocardial infarction ? 6 months prior to starting study drug10. LVEF < 45%11. Other clinically significant heart disease 12. A past medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome13. Patients who have not recovered from significant grade 3-4 side effects of previous antimyeloma therapy14. Patients who have undergone major surgery ? 2 weeks prior to starting study drug or who have not recovered from the side-effects of surgery15. Patients who have received any investigational drug ? 5 half lives prior to starting study drug or who have not recovered from side effects of such therapy. Or patients who have received previous investigational monoclonal antibody or radioimmunotherapy drug ? 60 days prior to starting study drug or who have not recovered from side effects of suchtherapy16. Known diagnosis of human immunodeficiency virus (HIV) infection17. Women of child-bearing potential (WCBP) who are pregnant or breast feeding. WCBP, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 24 consecutive months (i.e., who have had menses any time in the preceding 24 consecutive months), must have a negative serum pregnancy test ? 48 hours prior to starting study treatment. In addition, all sexually active WCBP and male patients must agree to use adequate contraceptive methods (oral,injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device;barrier contraceptive with spermicide; or vasectomized partner) throughout the study.18. Patients with a history of another primary malignancy that is currently clinicallysignificant or currently requires active intervention19. Patients unwilling or unable to comply with the protocol

Safety endpoints:? Occurrence of treatment-related dose-limiting toxicity (DLT) (ifobserved for doses up to 20 mg/kg) (Escalation phase ?phase I)? Occurrence of adverse drug reactions? Changes in the calcium and phosphate metabolism (PTH,Ca++, PO4--, Vit D3, calcitonin)? ImmunogenicityEfficacy endpoints:? Time to first SRE from randomization? Percent change from baseline in bone markers for boneresorption, metabolism, and formation? Anti-myeloma effect: changes in monoclonal protein in bloodand urine, changes in urinary light chain excretion, changes inserum free light chain, changes in plasma cells in bonemarrow (pre- vs. postreatment)? Change in number and size of lytic bone lesions on X-rayand/or MRI (pre- vs. postreatment)? Change in bone mineral density assessed by dual energy Xrayabsorptiometry and QCT (exploratory)? Change in bone strength in normal bone and osteolyticlesions assessed by QCT with finite element analysis(exploratory)? Change in circulating levels of TNF, IL-6, M-CSF and sCSF-1R (exploratory)

Fase II
  DISEÑO DEL ENSAYO:

Si
Si

No
No

Si
Si

No
Si
  COMPARADOR DEL ENSAYO CONTROLADO:

No
Si

No
No

Si

Centros participantes:

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

2
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:

7

Para estudios internacionales:

100
267

Investigadores

  INVESTIGADORES QUE PARTICIPAN EN EL ESTUDIO

Estado actual


 EC Finalizado



EC Finalizado