The rationale for this study design is based on the fact that the maximum tolerated dose (MTD) of single-agent ofatumumab and bendamustine have been previously determined. The choice of the doses for the combination is based on the investigators unpublished clinical experience, as well as inferred from extensive experimental data on the use of other monoclonal antibodies in combination chemotherapy in lymphoma patients. The starting dose of the 2 main component drugs is the MTD of each drug as single agent.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
50
* Ofatumumab (liquid concentrate for infusion in glass vials) infused iv on day 1 at 300 mg during the first cycle, followed by infusions of 1000 mg on day 1 of each subsequent cycle * Bendamustine (powder dissolved in sterile water) infused iv over 30-60 minutes at the dose of 120 mg/m2 (days 2,3 every 21 days) or 120 mg/m2(days 2,3 every 28) or 90 mg/m2 (days 2,3 every 28 days) depending on toxicity * Dexamethasone administered i.v. at 40 mg (days 1,2,3,4)
Fondazione IRCCS Istituto Nazionale Tumori
Milan, Italy
RECRUITINGOspedali Bianchi - Melacrino - Morelli
Reggio Calabria, Italy
RECRUITINGAdverse events (Phase I)
Incidence, severity, and attribution of treatment-emergent AEs
Time frame: 60 days after last dose of investigational drug
Complete Response rate (Phase II)
Response determined according to the revised response criteria for malignant lymphoma (Cheson, JCO 2008)
Time frame: 24 months
Duration of response (Phase II)
Duration estimated from the first confirmed tumor regression to the disease progression.
Time frame: At the screening, cycle 4 (12 weeks) , cycle 6 (18 weeks), 1 year Follow-up
Serial peripheral blood CD34+ cell counts
Time frame: Cycles 1 (3 weeks), 4 (12 weeks) and 6 (18 weeks)
Molecular analysis of CD34+ cells
Time frame: cycle 4 (12 weeks) or cycle 6 (18 weeks for inadequate harvests after cycle 4)
Serial molecular analysis of peripheral blood cells
Serial molecular analysis by PCR
Time frame: Cycles 1 (3 weeks), 4 (12 weeks) and 6 (18 weeks)
Ability to harvest ≥ 7 x106 CD34+ cells/kg
Time frame: Cycle 4 (12 weeks) or cycle 6 (18 weeks for inadequate harvests after cycle 4)
Presence of tumor cells in the peripheral blood
Monitored by morphology, immunophenotype and PCR
Time frame: Cycle 1 (3 weeks), 4 (12 weeks) and 6 (18 weeks)
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