Bortezomib (Velcade®): a feasibility and phase II study in childhood relapsed acute lymphoblastic leukemia
- Conditions
- Acute lymphoblastic leukemia (ALL)MedDRA version: 14.1Level: LLTClassification code 10063625Term: Acute lymphoblastic leukemia recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2009-014037-25-BE
- Lead Sponsor
- niversity Hospital Ghent
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 29
- Age between 6 months and 19 years
- patients with a second or subsequent relapsed ALL
- patients with first relapsed ALL after prior allogeneic stem cell transplantation in first complete remission
- patients with refractory first relapse of ALL, as defined by the ALL relapse protocol these patients were enrolled in begore
- circulating leukemic blasts of at least 100/ul peripheral blood (i.e. at least 0.1x109/l)
- patients must take adequate contraceptives when of childbearing potential
- written informed consent
Are the trial subjects under 18? yes
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
- relapse not involving bone marrow
- symptomatic CNS leukemia
- Active uncontrolled infection
- Performance status (Lansky or Karnofsky score) of 60% or less
- Life expectancy of less than 6 weeks
- Existing peripheral neuropathy NCI grade 2 or higher
- Presence of acute diffuse infiltrative and/or pericardial disease
- Existing clinical signs of cardiotoxicity
- Previous allogeneic stem cell transplantation within 100 days
- Pregnant or breastfeeding
- Other contra-indications for chemotherapy, including no recovery from previous treatment
- Previous exposure to bortezomib
- other experimental or conventional antileukemic treatment within 7 days from start of bortezomib
- allergy to boron and its metabolites
- concomitant anti-leukemic therapy other than according to this protocol
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Determine the antileukemic activity of combination chemotherapy including bortezomib as reinduction therapy in childhood relapsed/refractory ALL;Secondary Objective: - Determine the feasibility and safety of combining bortezomib with conventional combination chemotherapy in children and adolescents with relapsed/refractory ALL<br>- Evaluate bortezomib levels and proteasome inhibition in cerebrospinal fluid, bone marrow and peripheral blood in patients with relapsed/refractory ALL, and assess the relationship to the efficacy and toxicity of bortezomib;Primary end point(s): Antileukemic activity of bortezomib when added to dexamethasone and vincristine and intrathecal methotrexate, as determined by the absolute peripheral blood (PB) blast count on day 8 of treatment. Morphology will be centrally reviewed.;Timepoint(s) of evaluation of this end point: Day 8 of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Antileukemic activity of bortezomib when added to dexamethasone and vincristine and intrathecal methotrexate, as determined by the absolute bone marrow (BM) blast percentage on day 8, and BM and PB analysis on day 22 of treatment.<br>- Feasibility of combining bortezomib with dexamethasone and vincristine and intrathecal methotrexate, as determined by the percentage of patients in whom bortezomib had to be dose-reduced or withdrawn because of toxicity<br>- Toxicity of bortezomib when combined with dexamethoseand vincristine and intrathecal methotrexate, as determined by the percentage of patients suffering from grade III/IV toxicity in any field<br>- Determine the feasibility of combining second cycle of bortezomib with combination cheotherapy, its toxicity and antileukemic activity, as measured after 6 weeks of therapy by bone marrow, peripheral blood an cerebrospinal fluid;Timepoint(s) of evaluation of this end point: - Day 8 and 22 of treatment<br>- After 6 weeks of therapy