FDA Approves Ofatumumab for Additional CLL Patients

The Backstory

On January 19, 2016, the FDA approved the use of ofatumumab to treat patients with recurrent or progressive chronic lymphocytic leukemia (CLL) who are in complete or partial response following at least two prior treatment therapies.

This is the third time ofatumumab has received FDA approval for the treatment of patients with CLL. Ofatumumab was initially approved in 2009 for the treatment of patients with CLL who are refractory to fludarabine and alemtuzumab, and subsequently approved in April 2014 for use in combination with chlorambucil for previously untreated patients with CLL.

This approval is for the use of ofatumumab as a maintenance therapy. A maintenance therapy is an additional therapy that is administered to a patient after completion of an initial therapy in order to prolong the response achieved.

What is ofatumumab?

Ofatumumab is a human monoclonal antibody designed to target the CD20 molecules found on the surface of CLL cells and B-cell lymphocytes. CD20 molecules are found in over 90% of B-cell lymphomas. Ofatumumab is an immunotherapy that works by attaching itself to the CD20 molecule found on the surface of B-cells and directs the immune system to kill the cancerous B-cells.

Why was ofatumumab granted FDA approval?

Ofatumumab received this FDA approval based on the results from the PROLONG trial. In this phase III study, the use of ofatumumab as maintenance therapy was evaluated against no further treatment of patients who were in a complete or partial response after second or third line CLL treatment. The trial demonstrated an improvement in progression free survival for patients receiving ofatumumab maintenance of 29.4 months compared with 15.2 months for those on observation.

Were there any side effects?

Common side effects included infusion reactions, neutropenia, and upper respiratory tract infection. There were no unexpected, or new side effects observed for the patients receiving ofatumumab maintenance. The most common side effects seen were those previously described with ofatumumab infusions, including infusion reactions, low neutrophil counts, and infections.

How can you access ofatumumab now?

While all available trials for people with CLL at WCM have recently closed, our understanding of how best to use ofatumumab continues to increase. You can look to this space for further updates on CLL trials examining the use of ofatumumab.

A full list of trials open at WCM for patients with CLL is available on our Joint Clinical Trials website.

Dr. Richard Furman Discusses the Lessening of Infusion Reactions for CLL Patients Treated with Rituximab, Obinutuzumab, or Ofatumumab

In this video from OncLive, Director of the CLL Research Center, Richard R. Furman, M.D. discusses infusion reactions for  chronic lymphocytic leukemia (CLL) patients treated with anti-CD20 antibodies, including rituximab, obinutuzumab, and ofatumumab.

Ofatumumab Granted Breakthrough Therapy Designation for Untreated CLL

Recently, on September 13 the FDA granted a Breakthrough Therapy Designation to ofatumumab (Arzerra) in combination with chlorambucil for previously untreated patients with chronic lymphocytic leukemia (CLL) who are inappropriate for fludarabine-based therapy. This designation is awarded to drugs whose preliminary clinical evidence suggests an improvement over existing therapies on one or more clinically significant endpoints, speeding the bench to beside process. The designation was granted after preliminary results from a phase 3 clinical trial involving over 400 patients was announced in May.

Ofatumumab is a monoclonal antibody that targets an epitope on the CD20 molecule that encompasses parts of the small and large extra-cellular loops. The CD20 molecule is found on over 90% of B-cell lymphomas and assorted lymphoid tumors with a B-cell origin. Ofatumumab effectively kills cancer cells by directing the body’s immune system against normal and cancerous B-cells, and attaching to the CD20 molecule located on the surface of cancerous B-cells.

In addition to the aforementioned purposes, ofatumumab is being investigated for treatment in follicular lymphoma, diffuse large B-cell lymphoma, and Waldenstrom’s Macroglobulinemia.

Currently, there are ongoing ofatumumab trials at the Weill Cornell Lymphoma Program open to patients with CLL. Additional listings of clinical trials for CLL & SLL patients can be found here.

Please stay updated with our clinical trials listings for forthcoming trials involving ofatumumab and the Cornell Lymphoma Program website for further clinical research updates.

New Clinical Trial: Ofatumumab and Bortezomib in Untreated Waldenstrom Macroglobulinemia

A Multicenter Phase II Study of Ofatumumab and Bortezomib (OB) in Previously Untreated Patients with Waldenström Macroglobulinemia

Update: this study is closed to enrollment. 
The Weill Cornell Lymphoma Program is now enrolling patients in a new clinical trial for people with Waldenstrom Macroglobulinemia who have not been treated. The study sponsor is the National Comprehensive Cancer Network (NCCN). The principal investigator at Weill Cornell is Dr. Peter Martin.

For more information about the study, please call Amelyn Rodriguez, RN at (212) 746-1362 or email Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women age 18 and older
  • Diagnosis of Waldenstrom Macroglobulinemia (WM)
  • No prior anti-neoplastic therapy for WM
  • Detailed eligibility reviewed when you contact the study team

Study Details

Although there is currently no standard treatment for first-line management of WM, most clinicians and investigators believe that anti-CD20 directed therapy should compromise part of the regimen. Because it was the first therapeutic monoclonal antibody approved by the FDA , rituximab has been evaluated more than any antibody and has shown modest effects with limited toxicity. However, new treatments for WM are needed.

Ofatumumab has been approved for treatment of relapsed/refractory Chronic Lymphocytic Leukemia (CLL). It is an anti-CD20 monoclonal antibody that compared favorably to rituximab in a recent Phase 2 trial in patients with WM.

The purpose of the study is to determine how well previously untreated people with Waldenstrom Macroglobulinemia respond to treatment with ofatumumab in combination with bortezomib (Velcade). The study will also evaluate the safety of ofatumumab in combination with bortezomib.

Treatment Plan

Study participants will have four 28-day cycles of induction phase therapy. Participants will receive treatments weekly for three weeks, and then have a rest period (no treatment) for the fourth week. After the four cycles, there will be 4 weeks of no therapy and then 4 cycles of maintenance phase therapy. The maintenance cycles will be 28 days long. Participants will receive three weeks of treatment, then a resting period (no treatment) for the fourth week. This will be followed by four weeks of rest (no treatments). Then a new cycle will begin. Thus a new cycle of maintenance treatment will begin every 8 weeks. The entire period for both induction and maintenance therapy will be 1 year (52 weeks).

Participants will be followed until disease progression or 5 years from study entry, whichever comes first.

New Weill Cornell Study: Ofatumumab in Untreated Follicular Lymphoma

CALGB 50901: A Phase II Trial of Ofatumumab (CALGB IND #112390) in Previously Untreated Follicular Non-Hodgkin’s Lymphoma (NHL)

The Weill Cornell Lymphoma Program is now enrolling people in a new clinical trial for patients with follicular non-Hodgkin lymphoma. Dr. Peter Martin is the physician leading the study at Weill Cornell.

For more information about the study, please call Amelyn Rodriguez, RN at (212) 746-1362 or email Amelyn at amr2017@med.cornell.edu.

Key Eligibility
  • Men and women age 18 or older
  • Follicular non-Hodgkin lymphoma (NHL)
  • No prior therapy for NHL including chemotherapy or immunotherapy
  • Detailed eligibility reviewed when you contact the study team
Study Details

This is a clinical trial for patients with follicular non-Hodgkin lymphoma (NHL) who have not been previously treated. The purpose of the study is to determine how well patients with follicular NHL respond to treatment with the drug ofatumumab.

Ofatumumab is an antibody therapy that is targeted to attack the abnormal cancer cells that make up follicular lymphoma by recognizing a protein on the surface of these cells. Ofatumumab is an effective treatment for follicular lymphoma and chronic lymphocytic leukemia that comes back after people first respond to other chemotherapy. It is not known how well ofatumumab will work in patients with follicular lymphoma who have not been previously treated.

All patients in the study will receive ofatumumab. You will be randomly assigned to receive one of two doses of ofatumumab; neither you nor the study physician can choose which dose you receive.  You will receive either 500 mg or 1000 mg of the study drug via infusion on days 1, 8, 15 and 22 during the first 4 weeks of treatment (induction therapy). Following induction therapy ofatumumab will be given every other month to cover a total of 9 months. During this time you will continue to receive the same dose, either 500 mg or 1000 mg, that you were initially assigned.

We expect patients to be receiving treatment in the study for approximately 9 months. After completing study treatment you will be asked to return for follow-up tests 11, 15, 19, 23, 27, 31, and 35 months after entering the study, and then every 6 months for a maximum of 10 years from study entry, unless your disease should return.


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