Clinical Trials, Crossover, and Clinical Equipoise: A Patient's Perspective


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I am writing with regard to two articles on the ethical imperative of clinical equipoise written by Susan O’Brien, MD, and Stephen J. Schuster, MD, and published recently in The ASCO Post.1,2 I was a victim of Pharmacyclics’ policies during one of their randomized ibrutinib trials (PCI-32765) conducted in 2012.

I was diagnosed with chronic lymphocytic leukemia (CLL) in 2002. Following a slow disease progression (CLL with a 13q deletion), I was treated with fludarabine, cyclophosphamide, and rituximab (Rituxan) during 2008 under the direction and protocol of physicians at The University of Texas MD Anderson Cancer Center in Houston, and Lehigh Valley Hospital in Allentown, Pennsylvania.

I achieved complete remission, which lasted for approximately 3 years until October 2011, when my CLL returned with a more aggressive form (17p deletion and p53 inactivation). At that point, I started my research again to determine the latest and greatest treatment developments and options for patients with CLL.

With information and guidance from a number of experts in the field, I decided to enroll in a Pharmacyclics-sponsored ibrutinib trial. I initially qualified for a phase III randomized trial of ibrutinib vs ofatumumab (Arzerra) with John Byrd, MD, at Ohio State University, but finally entered the trial with Dr. Schuster at the University of Pennsylvania (UPenn).

At UPenn, I was assigned to the ofatumumab arm of the trial. I received 8 weekly ofatumumab infusions during August/September 2012. The ofatumumab treatment did not work, and I was left with a packed bone marrow, multiple swollen lymph nodes, increasing cancerous lymphocytes, declining platelets, anemia, and neutropenia. I had become transfusion-dependent.

Understanding my dire condition, I contacted Pharmacyclics to request a crossover to ibrutinib, which at that point was showing extremely favorable results for the effective management of CLL with a significant remission rate. Pharmacyclics denied my request and further excluded me from participating in any other ibrutinib trials because I was already a “data point” in one of their trials.

The actual response from the now former Chief Medical Officer of Pharmacyclics, Inc, was, “We agreed that we would follow all patients enrolled in the PCYC-1112-CA (RESONATE) trial for several important endpoints, and one of these is overall survival. This means we cannot allow patients who are randomized to receive ofatumumab on the trial to receive ibrutinib.” 

In effect, Pharmacyclics told me that they had their data point from me and even if I died to achieve their “endpoint,” it was not their concern. In fact, a “dead” data point on ofatumumab furthered their case for fast-track FDA approval.

Pharmacyclics cited FDA regulations as the reason for their position on “compassionate use” for dying trial participants. I contacted the FDA specifically to ask about their strict regulations on the Pharmacyclics ibrutinib trials. The FDA told me that the decision to restrict and exclude access to ibrutinib for their clinical trial participants was entirely up to Pharmacyclics’ management. 

Something must be done for the ethical treatment of humans in an investigational environment. The FDA and the biopharmaceutical drug companies cannot simply turn a blind eye to clinical trial patients who will otherwise die without the compassionate use of the most promising treatments and cures for cancer.

Survival on transfusions and/or bone marrow transplant seemed to be my only options following my Pharmacyclics trial on ofatumumab. Fortunately, due to the incredible research led by Carl June, MD, and the professional medical team at UPenn, I underwent CART19 T-cell therapy from February to April 2013, and I am now in complete remission and back to living my life. ■

—Bob Levis
Allentown, Pennsylvania

References

1. O’Brien S: Ibrutinib CLL trial: Where is the equipoise? The ASCO Post 4(7):1, May 1, 2013.

2. Schuster SJ: The ethical imperative of clinical equipoise. The ASCO Post 4(7):25, May 1, 2013.



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