New Data on Horizon in Several Key Areas

Ben Leach
Published Online: Monday, December 3, 2012
Dr. Andrew D. Zelenetz

Andrew D. Zelenetz, MD, PhD

Although new therapies have revolutionized the management of certain hematologic malignancies during the past 15 years, clinical trials currently under way hold the potential to yield new targeted agents and better treatment strategies.

For insight into emerging strategies in this complex arena, OncologyLive touched base with Andrew D. Zelenetz, MD, PhD, chief of Lymphoma Service and vice chairman of Medical Informatics at Memorial Sloan-Kettering Cancer Center in New York City. He helped develop several of the new agents approved for the treatment of lymphoma, including bortezomib (Velcade), and continues to play a leading role in ongoing clinical trials.

Zelenetz serves as program director of the 17th Annual International Congress on Hematologic Malignancies, scheduled for February 15-17, 2013, in New York City, where experts will discuss the implications of research advances. The congress is hosted by Physicians’ Education Resource (PER).

Speaking in advance of the American Society of Hematology (ASH) meeting, scheduled for December 8-11 in Atlanta, Georgia, Zelenetz discussed several new agents in development and recent trends he finds significant.

Ibrutinib Study Results Slated for Release

The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib, which promotes apoptosis and inhibits cell migration and adhesion, is being explored in several different hematologic malignancies. It is the most developed of a group of new agents under study in chronic lymphocytic leukemia (CLL), where the FDA has granted Fast Track designation in patients with relapsed or refractory disease after at least one prior therapy.

Zelenetz said that the drug has demonstrated dramatic activity in CLL, noting that data presented earlier this year confirmed its activity and paved the way for important studies yet to come.

At the European Hematology Association (EHA) Congress in June, the results were presented from a phase IB/II study that evaluated singleagent ibrutinib in patients who were either treatmentnaïve or relapsed/refractory after at least two lines of therapy. The observed overall response rate for patients who had received a 420-mg daily dose of ibrutinib was 67% in patients who were relapsed or refractory at a median follow-up of 12.6 months, and 73% among treatmentnaïve patients at a median follow-up of 10.7 months.1

Pharmacyclics, the company developing ibrutinib, announced that updates on this trial as well as eight others involving the agent have been accepted for presentation during ASH 2012. The company’s clinical development program involves a variety of hematologic malignancies (Table).2

Table. Ongoing Clinical Trials of Ibrutinib (PCI-32765)

Main Malignancy Typea Description Status
B-cell lymphoma Dose-escalation study Phase I (NCT00849654)
B-cell lymphoma
Chronic lymphocyctic leukemia
Safety, fixed-dose study Phase I (NCT01109069)
Chronic lymphocyctic leukemia
Small lymphocytic lymphoma
Safety, optimal-dose study

Ibrutinib plus fludarabine/ cyclophosphamide/rituximab vs ibrutinib plus bendamustine/rituximab

Ibrutinib plus ofatumumab
Phase I/II (NCT01105247)

Phase I/II (NCT01292135)

Phase I/II (NCT01217749)
Diffuse large B-cell lymphoma Safety, efficacy study Phase II (NCT01325701)
Mantle cell lymphoma Monotherapy for 2 cohorts: Patients who failed bortezomib and patients who are bortezomib-naïve Phase II (NCT01236391)
Multiple myeloma Safety, clinical benefit rate at 3 different dosages, with and without dexamethasone Phase II (NCT01478581)

aSome trials include related hematologic malignancies.

Sources
Clinical trials overview. Pharmacyclics website, pharmacyclics.com. Accessed November 6, 2012.
ClinicalTrials.gov website. ClinicalTrials.gov. Accessed November 6, 2012.

Of these studies, Zelenetz highlighted a diffuse large B-cell lymphoma (DLBCL) trial as one that could potentially change treatment. The phase II trial is evaluating whether ibrutinib has preferential activity in the ABC subtype of relapsed/refractory DLBCL.

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