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.

Conditions: Mieloma Múltiple refractario o en recaída.
MedDRA version: 9.1Level: LLTClassification code 10028228Term: Multiple myeloma

Registration Number: EUCTR2008-000411-15-ES

Lead Sponsor: ovartis Farmacéutica, S.A

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 267

Inclusion Criteria

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 or
measurable urine M-protein must have measurable increased concentrations of free light
chains (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 fracture
5. Stable renal function defined as two serum creatinine determinations of < 2.5 mg/dl or
calculated (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 acid
7. No symptoms of hyperviscosity, amyloidosis or recurrent infection
8. Corrected serum calcium < 12 mg/dl or ionized calcium < 6.5 mg/dL within 14 days prior
to registration
9. Life expectancy of at least 12 months.
10. Ambulatory patients aged 18 years or older
11. ECOG performance status ? 2
12. Absolute neutrophil count ? 1500/mm3
13. Platelet count ? 75,000/mm3
14. Hemoglobin (Hgb) ? 9 g/dl (prior RBC transfusion, recombinant epoetin alfa, or
darbepoetin alfa allowed)
15. Electrolyte levels ? LLN (i.e., potassium, magnesium, phosphorus) correction with
supplements allowed
16. AST and ALT ? 2.5 x ULN
17. Serum bilirubin ? 1.5 x ULN
18. Patients must sign the informed consent form and be willing and able to comply with the
study protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Known concomitant disease(s) known to influence Ca2+ metabolism including
hyperparathyroidism, 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 mouth
4. Patients who are allergic to/ intolerant of bisphosphonate therapy
5. Acute or chronic liver disease
6. Patients with any peripheral neuropathy ? CTCAE grade 2
7. Other concurrent severe and/or uncontrolled concomitant medical conditions that could
cause unacceptable safety risks or compromise compliance with the protocol
8. Angina pectoris ? 3 months prior to starting study drug
9. Acute myocardial infarction ? 6 months prior to starting study drug
10. 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 syndrome
13. Patients who have not recovered from significant grade 3-4 side effects of previous antimyeloma therapy
14. Patients who have undergone major surgery ? 2 weeks prior to starting study drug or who have not recovered from the side-effects of surgery
15. 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 such
therapy
16. Known diagnosis of human immunodeficiency virus (HIV) infection
17. 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 clinically
significant or currently requires active intervention
19. Patients unwilling or unable to comply with the protocol