A study to compare masitinib in combination with bortezomib and dexamethazone to placebo in combination with bortezomib and dexamethazone in the treatment of patients with relapsing multiple myeloma

Phase 1

• Conditions: Multiple Myeloma relapsing after one previous line therapy; MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2009-017930-35-DE
• Lead Sponsor: AB Science

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-11-18
• Last Update Posted: 8 March 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Patient with confirmed multiple myeloma requiring systemic
therapy. All three criteria must be met:
•Clonal bone marrow plasma cells > 10%
•Presence of serum and/or urinary monoclonal protein
•Evidence of end-organ damage that can be attributed to
the underlying plasma cell proliferative disorder, specifically:
oHypercalcemia: serum calcium > 11.5 mg/100 ml or
o Renal insufficiency: serum creatinine > 173 µmol/l
oAnemia: normochromic, normocytic with a hemoglobin
value of > 2g/100 ml below the lower limit of normal or a
hemoglobin value < 10g/100 ml
oBone lesions: lytic lesions, severe osteopenia or pathologic
fractures
2. Patient with multiple myeloma relapsing according to the International uniform response criteria for multiple myeloma (IMWG 2009/ revised Bladé criteria) (defined in Table 5) to one previous line of treatment (defined in Table 6). Patients previously treated, with Bortezomib, for multiple myeloma can be included if and only if :
o they have shown minimal, partial or complete response to this treatment
o they have not been refractory to this treatment (to be considered as bortezomib refractory patient, any patient who didn’t show any response to previous bortezomib treatment or whose disease progressed during or within 60 days of bortezomib treatment)
3. Patient candidate for receiving the standard therapy
(bortezomib and dexamethazone)
4. Patient with measurable progressive disease defined by at
least one of the following two measurements:
•Serum M-protein = 1 g/dL
•Urine M-protein = 200 mg/24h
5. Patient with ECOG = 2
6. Patient with adequate organ function
o Absolute neutrophils count (ANC) = 1.5 x 109/L
o Haemoglobin = 10 g/dL
o Platelets (PTL) = 75 x 109/L
o AST/ALT = 3x ULN (= 5 x ULN in case of liver metastases)
o Gamma GT = 2.5 x ULN (= 5 x ULN in case of liver metastases)
o Bilirubin = 1.5x ULN (= 3 x ULN in case of liver metastases)
o Creatinine clearance = 30 mL/min (Cockcroft and Gault formula)
o Albuminaemia = 1 LLN
o Urea = 2 ULN
o Albuminuria = 300 mg/24 hours
7. Patient with life expectancy > 6 months
8. Man or non-pregnant non-lactating woman, age >18 years
and weight > 40 Kgand BMI > 18 kg/m²
9. Man and woman of childbearing potential, (entering the
study after a menstrual period and who have a negative
pregnancy test) must agree to use two methods (one for
the patient and one for the partner) of medically acceptable
forms of contraception during the study and for 3 months
after the last treatment intake.
10. Patient able and willing to comply with study procedures as
per protocol
11. Patient able to understand, sign, and date the written informed consent form at screening visit prior to any
protocol-specific procedures are performed. If the patient is deemed by the treating physician to be cognitively
impaired or questionably impaired in such a way that the ability of the patient to give informed consent is
questionable, the designated legal guardian must sign the informed consent.
12. Patient able to understand the patient card and to follow the patient card procedures in case of
signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months.

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes

Exclusion Criteria

1. Patient with peripheral neuropathy Grade >2
2. Patient with hypersensitivity to bortezomib, boron or
dexamethazone
3. Patient whose disease progressed during or within 60 days of
bortezomib treatment or of any other Multiple Myeloma
therapy
4. Patient who received bortezomib within 6 months of
randomisation to this study.
5. Past discontinuation of bortezomib due to associated grade 3
or higher adverse event.
6. Patient with contra-indication to high dose of steroids
(including ongoing active infection, use of live vaccines, virosis
such as hepatitis, herpes, varicella, herpes zoster).
7. Patient with acute diffuse infiltrative pulmonary and pericardial
disease
8. Patient treated for a cancer other than multiple myeloma
within five years before enrolment, with the exception of basal
cell carcinoma and cervical cancer in situ
9. Patient with central nervous system (CNS) metastasis or with
history of CNS metastasis
10. Patient with one of the following cardiac conditions:
•Patient with recent cardiac history (within 6 months) of:
-Acute coronary syndrome
-Acute heart failure (class III or IV of the NYHA classification)
-Significant ventricular arrhythmia (persistent ventricular
tachycardia, ventricular fibrillation, resuscitated sudden
death)
•Patient with cardiac failure class III or IV of the NYHA
classification
•Patient with severe conduction disorders which are not
prevented by permanent pacing (atrio-ventricular block 2
and 3, sino-atrial block)
•Syncope without known aetiology within 3 months
•Uncontrolled severe hypertension, according to the
judgment of the investigator, or symptomatic hypertension
11. Patient with history of poor compliance or history of
drug/alcohol abuse, or excessive alcohol beverage
consumption that would interfere with the ability to comply
with the study protocol, or current or past psychiatric
disease that might interfere with the ability to comply with
the study protocol or give informed consent

Previous treatments
12. High dose of corticosteroids and/or local irradiation should
be stopped at least 2 weeks prior to Baseline
13. Administration of any other treatment for multiple myeloma
should be stopped at least 4 weeks prior to Baseline.
Patients who received bortezomib within 6 months prior to
Baseline are excluded
14. Treatment with any investigational agent should be stopped
at least 4 weeks prior to Baseline
15. Patient eligible for bone-marrow transplantation as second
line therapy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified