Highlights of the NCCN Oncology Research Program

The NCCN Oncology Research Program (ORP) strives to improve the quality of life for patients and reduce cancer-related deaths by advancing cancer therapies through research. Since the program’s establishment in 1999, the NCCN ORP has brought millions of dollars in research grants to investigators at NCCN Member Institutions. Research grants are provided to NCCN through collaborations with pharmaceutical and biotechnology companies; these grants are in turn used to support scientifically meritorious cancer research efforts.

NCCN ORP studies typically explore new avenues of clinical investigation and seek answers to important cancer-related questions. All studies are approved and funded through a scientific peer-review process and are overseen by the ORP.

NCCN studies funded through the grant mechanism are highlighted below.

A Phase II Study of Ofatumumab/High-Dose Methylprednisolone Followed by Ofatumumab/Alemtuzumab in 17p Deletion Chronic Lymphocytic Leukemia

Principal Investigator: Jennifer R. Brown, MD, PhD

Conditions: Chronic lymphocytic leukemia and small lymphocytic lymphomas

Institutions: Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center, with future participation from University of Rochester

This study will be a parallel 2-arm phase II multicenter study in participants with 17p deletion chronic lymphocytic leukemia (CLL) who require therapy. Participants will be assigned to 1 of 2 treatment cohorts based on whether they have previously untreated CLL/small lymphocytic lymphoma (SLL) or have had any prior systemic therapy. Therapy is the same in both cohorts and will include ofatumumab with high-dose methylprednisolone (HDMP) for 2 to 4 cycles (Part A) followed by ofatumumab with alemtuzumab for 12 to 24 weeks to maximum response (Part B). The trial therapy is designed to prepare eligible patients for reduced-intensity allogeneic stem cell transplant (SCT), and includes a maintenance phase for those who are not transplant candidates.

Primary Objective:

• Determine the overall response rate (ORR) at the conclusion of 2-part induction therapy with ofatumumab/HDMP (Part A) followed by ofatumumab/alemtuzumab (Part B) in 2 cohorts of participants with 17p deletion: those with previously untreated versus relapsed/refractory CLL/SLL.

Secondary Objectives:

• Determine the complete response (CR) rate, rate of objective response by disease compartment (nodes/spleen, cytopenias/bone marrow), rate of minimal residual disease (MRD) negativity by 4-color flow cytometry, progression-free survival (PFS), and overall survival (OS) for induction therapy with ofatumumab/HDMP followed by ofatumumab/alemtuzumab in each cohort.

• 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 2 cycles of ofatumumab/HDMP. To determine the number of participants eligible to stop ofatumumab/HDMP after 2 cycles, and the number who complete 2 versus 4 cycles.

• Determine the improvement in ORR, CR rate, and the rate at which MRD negativity is achieved in bone marrow with ofatumumab/alemtuzumab, following initial ofatumumab/HDMP.

• Determine the improvement in ORR, CR rate, and the rate of MRD negativity, and the rate of detectable MRD recurrence or frank relapse during maintenance ofatumumab/alemtuzumab in those participants not eligible for or willing to undergo allogeneic SCT.

• Determine the rate at which transplant-eligible participants are able (and willing) to proceed to allogeneic SCT for consolidation of remission.

• Assess the safety of ofatumumab/HDMP followed by ofatumumab/alemtuzumab in each cohort, and the safety of ofatumumab/alemtuzumab consolidation.

Contacts: Jennifer R. Brown, MD, PhD • 617-632-4564 • jennifer_brown@dfci.harvard.edu

Caitlin Tesmer • 617-632-6940 • ctesmer1@partners.org

ClinicalTrials.gov Identifier: NCT01465334