Clinical trial NCT01491841
Conditions: Non-Hodgkin's Lymphoma
Sponsor: Anne Beaven, MD
Start date: 2011-11-01; Completion date: 2017-02-17
Enrollment: 33 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a phase I trial of the combination of bendamustine, rituximab and pixantrone in patients with relapsed/refractory B cell non-Hodgkin lymphoma. A standard 3+3 design will be used to determine the maximum tolerated dose (MTD) of the combination. A static dose of bendamustine and rituximab will be used and the dose of pixantrone will be escalated in each cohort. Pixantrone will be dosed on a 21 day cycle at 55mg/m2, 85mg/m2, and 115mg/m2 in sequential cohorts dependent on acceptable toxicity profile at each dose level. MTD will be determined based on DLTs that occur during the first 2 cycles of the drug combination.

Phase II did not proceed as planned due to withdrawal of pixantrone from the US.

Detailed description:
This is a phase I trial utilizing a traditional 3+3 design to evaluate maximum tolerated dose (MTD) and optimal dose schedule of pixantrone in combination with bendamustine (120mg/m2 on day 1 of each 21 day cycle) and rituximab (375mg/m2 on day 1 of each 21 day cycle). No patients will be entered on an escalated dosage level until at least 3 patients have been treated at the previous level and assessed for a dose limiting toxicity. Dose levels will be escalated in cohorts of 3 patients as long as no drug-related DLT occurs in the first 2 cycles. If one patient is observed to suffer a DLT, this cohort will be expanded to include at least 6 patients total. If less than 2 patients in the expanded cohort of 6 patients experience a DLT, dose escalation will resume. If 2 of 6 patients enrolled at the same dose level experience a DLT, the MTD has been exceeded, and the dose escalation will cease. The next lower dose will be considered the MTD. If any patient withdraws from the study prior to completing 2 cycles for reasons other than a DLT then that patient will be replaced in order to determine the MTD.

If dose limiting toxicity is observed at the initial dose level in 2 patients, the MTD has been exceeded and the starting dose level will be reduced to 25mg/m2. If 1 patient experiences a DLT in the -1 dose range, the cohort will be expanded to at least 6 patients. If a second patient experiences a DLT at the -1 dose level, the trial will be closed.

For part 1, those who have a confirmed diagnosis of relapsed/refractory B cell non-Hodgkin's lymphoma of any subtype will be considered eligible for enrollment. Each cycle will be 21 days. Subjects will be assessed for DLTs during the first 2 cycles of study drug. They will be assessed for response after cycle 2. Patients not experiencing a DLT during the first 2 cycles and who have stable disease or better may continue to receive up to 6 cycles of treatment with the triplet combination. If any patient withdraws from the study prior to completing 2 cycles for reasons other than a DLT then that patient will be replaced in order to determine the MTD.

Phase II did not proceed as planned due to withdrawal of pixantrone from the US.

Arms: arm 1: Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 55mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle arm 2: Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 85mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle arm 3: Bendamustine, 120mg/m2; administered first on Day 1 of each cycle. Rituximab, 375mg/m2; administered second on Day 1 of each cycle. Pixantrone, 115mg/m2; to be administered last, 4-6 hours after bendamustine, on Day 1 of each cycle Pegfilgrastim, 6mg; administered on Day 2 of each cycle
Interventions: intervention 1: Bendamustine + Rituximab + Pixantrone intervention 2: Pegfilgrastim
Intervention descriptions: intervention 1: Dose escalation of pixantrone (55mg/m2, 85mg/m2 and 115mg/m2) in combination with static dose bendamustine (120mg/m2 on Day 1 of each 21 day) and rituximab (375mg/m2 on Day 1 of each 21 day cycle). intervention 2: 6mg administered on Day 2 of each 21 day cycle

Protocol documents: