Clinical Trial: Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase II Study of Ofatumumab-High Dose Methylprednisolone Followed by Ofatumumab-Alemtuzumab in 17p Deletion CLL

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 Summary:

There are three possible components to the treatment in this study:

Part A - Ofatumumab + HDMP

• A maximum of 4 cycles of 28 days. Ofatumumab and HDMP will be given intravenously. Ofatumumab will given on days 1, 8, 15 and 22. HDMP will given on days 1, 2, and 3.

Part B - Ofatumumab + Alemtuzumab

• Subjects who have not experienced a Complete Response with no residual detectable disease after Part A will continue on to Part B.
• A maximum of 6 cycles of 28 days. Ofatumumab will be given intravenously on day 1 and Alemtuzumab will be given as a subcutaneous (under the skin) injection on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26.

Part C - Maintenance with Ofatumumab + Alemtuzumab

• Subjects who have experienced at least stable disease in Parts A and B can continue on to Part C. Subjects who are eligible may instead proceed to stem cell transplantation after Parts A and B.
• Part C is a maximum of 26 cycles of 28 days. Ofatumumab will be given intravenously every other cycle. Alemtuzumab will be given as a subcutaneous injection every 14 days.

During all cycles subjects will also have clinical exams, and blood tests; imaging tests (CT scans), bone marrow aspirate and biopsy, and serum pregnancy tests (if applicable) will occur at various intervals.

Current Primary Outcome: Overall Response Rate (ORR) [ Time Frame: 2 years ]

Original Primary Outcome: ORR [ Time Frame: 2 years ]

Current Secondary Outcome:

• Complete response (CR) Rate [ Time Frame: 2 years ]
  To determine the CR rate, rate of objective response by disease compartment (nodes/spleen, cytopenias/bone marrow) rate of MRD negativity by four color flow cytometry, PFS and OS for induction therapy with ofatumumab-HDMP followed by ofatumumab-alemtuzumab in each cohort.
• ORR, CR Rate [ Time Frame: 2 years ]
  To determine the ORR, CR rate, rate of objective response by disease compartment (nodes/spleen, cytopenias/bone marrow) and rate of Minimal Residual Disease (MRD) negativity at the conclusion of ofatumumab-HDMP; and at earlier interim analysis after two cycles of ofatumumab-HDMP. To determine the number of participants eligible to stop ofatumumab-HDMP after two cycles, as well as the number who complete two versus four cycles.
• Improvement in ORR, CR rate [ Time Frame: 2 years ]
  To determine the improvement in ORR, CR rate and the rate at which MRD negativity is achieved in bone marrow with ofatumumab-alemtuzumab, following initial HDMP-ofatumumab.
• Improvement in ORR, CR Rate during maintenance [ Time Frame: 2 years ]
  To determine the improvement in ORR, CR rate and rate of MRD negativity, as well as the rate of detectable recurrence of MRD or frank relapse, during maintenance ofatumumab-alemtuzumab in those participants not eligible for or willing to undergo allogeneic SCT.
• Rate of subjects proceeding to transplant [ Time Frame: 2 years ]
  To determine the rate at which transplant-eligible participants are able (and willing) to proceed to allogeneic SCT for consolidation of remission.
• Safety [ Time Frame: 2 years ]
  To assess the safety of ofatumumab-HDMP followed by ofatumumab-alemtuzumab in each cohort, and the safety of ofatumumab-alemtuzumab consolidation. All participants receiving investigational agents will be evaluated for safety. The safety parameters include all laboratory tests and hematological abnormalities, physical examination findings, and spontaneous reports of adverse events and serious adverse events reported to the investigator by participants. All toxicities encountered during the study will be evaluated according to the NCI criteria and recorded prior to each course of therapy.

Original Secondary Outcome:

• CR Rate [ Time Frame: 2 years ]
  To determine the CR rate, rate of objective response by disease compartment (nodes/spleen, cytopenias/bone marrow) rate of MRD negativity by four color flow cytometry, PFS and OS for induction therapy with ofatumumab-HDMP followed by ofatumumab-alemtuzumab in each cohort.
• ORR, CR Rate [ Time Frame: 2 years ]
  To determine the ORR, CR rate, rate of objective response by disease compartment (nodes/spleen, cytopenias/bone marrow) and rate of MRD negativity at the conclusion of ofatumumab-HDMP; and at earlier interim analysis after two cycles of ofatumumab-HDMP. To determine the number of participants eligible to stop ofatumumab-HDMP after two cycles, as well as the number who complete two versus four cycles.
• Improvement in ORR, CR rate [ Time Frame: 2 years ]
  To determine the improvement in ORR, CR rate and the rate at which MRD negativity is achieved in bone marrow with ofatumumab-alemtuzumab, following initial HDMP-ofatumumab.
• Improvement in ORR, CR Rate during maintenance [ Time Frame: 2 years ]
  To determine the improvement in ORR, CR rate and rate of MRD negativity, as well as the rate of detectable recurrence of MRD or frank relapse, during maintenance ofatumumab-alemtuzumab in those participants not eligible for or willing to undergo allogeneic SCT.
• Rate of subjects proceeding to transplant [ Time Frame: 2 years ]
  To determine the rate at which transplant-eligible participants are able (and willing) to proceed to allogeneic SCT for consolidation of remission.
• Safety [ Time Frame: 2 years ]
  To assess the safety of ofatumumab-HDMP followed by ofatumumab-alemtuzumab in each cohort, and the safety of ofatumumab-alemtuzumab consolidation. All participants receiving investigational agents will be evaluated for safety. The safety parameters include all laboratory tests and hematological abnormalities, physical examination findings, and spontaneous reports of adverse events and serious adverse events reported to the investigator by participants. All toxicities encountered during the study will be evaluated according to the NCI criteria and recorded prior to each course of therapy.

Dates:
Date Received: October 18, 2011
Date Started: November 2011
Date Completion: December 2020
Last Updated: October 25, 2016
Last Verified: October 2016