Clinical trial NCT01465334
Conditions: CLL SLL
Keywords: 17p Deletion CLL
Sponsor: Dana-Farber Cancer Institute
Start date: 2011-12-01; Completion date: 2017-01-01
Enrollment: 30 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The main purpose of this study is to examine how two separate groups of 17p deletion Chronic lymphocytic leukemia (CLL) participants respond to sequential treatment with this particular combination of drugs. The two groups are those participants who have previously received treatment for their CLL and those who have not yet received any treatment. The combination of drugs is Ofatumumab and High-Dose Methylprednisolone (HDMP) first followed by Ofatumumab and Alemtuzumab. All three drugs are FDA approved and have known activity in treating 17p CLL. We hope that by combining these drugs together in this study, they will have more benefit than each one alone and that the subjects' CLL will be significantly impacted.

Detailed description:
Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy.

Part A: Ofatumumab + HDMP 2-4 cycles Part B: Ofatumumab + Alemtuzumab 1-6 cycles Part C: Maintenance with Ofatumumab + Alemtuzumab up to 2 years

Between days 15-22 of Cycle 2 of Part A, participants are restaged. Participants who achieve nodal complete response discontinue Part A therapy and undergo minimal residual disease (MRD) assessment to guide the decision whether to go to Part B or Part C. The participants with persistent disease after 2 cycles of Part A therapy receive 2 more cycles of Part A therapy and then undergo another restaging as well as MRD assessment. At restaging, participants with minimal disease are eligible for Part C or allogeneic stem cell transplant (SCT) off protocol. The remaining participants receive Part B therapy. On Part B, restaging occurs at weeks 12 and 18. If MRD negative complete response (CR) status is achieved then therapy is discontinued and the primary endpoint evaluation occurs 2 months later. Otherwise with persistent disease Part B therapy continues up to 24 weeks and the primary endpoint evaluation occurs after Part B therapy is completed. Participants who achieve clinical complete response may receive Part C therapy or be observed while waiting SCT.

Arms: arm 1: Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days):

Induction Part A: Ofatumumab + HDMP 2-4 cycles

Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22

High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3

Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy.

Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles

Ofatumumab: 1000 mg IV Day 1

Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26

Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study.

Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles

Ofatumumab: 1000 mg IV Day 1 every other cycle

Alemtuzumab: 30 mg subcutaneously Days 14, 28 arm 2: Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days):

Induction Part A: Ofatumumab + HDMP 2-4 cycles

Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22

High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3

Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy.

Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles

Ofatumumab: 1000 mg IV Day 1

Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26

Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study.

Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles

Ofatumumab: 1000 mg IV Day 1 every other cycle

Alemtuzumab: 30 mg subcutaneously Days 14, 28
Interventions: intervention 1: Ofatumumab intervention 2: High-Dose Methylprednisolone intervention 3: Alemtuzumab
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents: