Tag: cancer clinical trials

ASCO 2013: Ibrutinib Combined with R-CHOP Shows Positive Results in Patients with CD20-positive, B-cell non-Hodgkin Lymphoma

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By Jia Ruan, MD, PhD

Ibrutinib is a first-in-class oral Bruton’s tyrosine kinase inhibitor that has shown promise in treating a variety of relapsed and refractory B-cell malignancies. At the 2013 meeting of the American Society of Clinical Oncology in Chicago, Dr. Anas Younes of the MD Anderson Cancer Center presented results from a recent phase 1b trial combining ibrutinib with standard doses of R-CHOP in patients with previously untreated CD20 positive NHL (NCT01569750).

A total of seventeen patients were enrolled, including those with subtypes of diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma. The recommended phase 2 dose of ibrutinib was established at 560 mg daily in combination with standard doses of R-CHOP given every 21 days.  The overall response rate of treatment was 100% with 7 complete and 3 partial responses in 10 evaluable patients. The most common adverse events were neutropenia (77%), thrombocytopenia (65%), vomiting (59%), anemia (53%), nausea (47%), fatigue (35%), headaches (29%), constipation (24%), diarrhea (24%), and dizziness (24%).

The study concluded that this novel combination of Ibrutinib and R-CHOP has an acceptable and expected safety profile.  An expansion cohort 560 mg ibrutinib is being opened to further explore the safety and efficacy of IR-CHOP in patients with newly diagnosed diffuse large B-cell lymphomas.

For a full listing of all current clinical trials underway in the Lymphoma Program, please click here.

Ibrutinib is Effective Therapy for Patients with Previously Treated Mantle Cell Lymphoma

On June 20, 2013, the exciting results of a phase 2 clinical trial of ibrutinib in patients with previously treated mantle cell lymphoma (MCL) were published in the New England Journal of Medicine. Ibrutinib is an oral inhibitor of Bruton’s Tyrosine Kinase (BTK), an enzyme that plays a critical role in the survival and growth of some lymphomas, including MCL, CLL/SLL, follicular lymphoma, DLBCL, and Waldenstrom’s macroglobulinemia.

In this trial, 111 patients with MCL received oral ibrutinib at a dose of 560 mg daily. Despite a high number of prior therapies, 68% of patients experienced a significant response to ibrutinib, including 21% of patients experiencing a complete response. The estimated average response duration was almost 18 months. Overall, the treatment was well tolerated. The study authors concluded that ibrutinib is highly effective in treating relapsed and refractory MCL, achieving responses comparable to intensive chemotherapy regimens with less toxicity. Weill Cornell’s Dr. Peter Martin, one of the study’s lead authors, commented, “It has been tremendously gratifying to be able to offer ibrutinib to our patients with mantle cell lymphoma. We are all working hard so that this drug can be made available to all patients in the near future.”

The Lymphoma Program at Weill Cornell will be participating in an early access trial that will help provide ibrutinib to patients with MCL pending its official FDA approval.  Look to this space for further updates.

ASCO 2013: Effectiveness of Entecavir and Lamivudine in Preventing Reactivation of Hepatitis B in HBsAg-Positive Patients with Untreated DLBCL

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By Peter Martin, MD

Patients with DLBCL and a history of hepatitis B are at increased risk from the reactivation of a viral infection following treatment with R-CHOP. Many guidelines recommend that patients at risk of hepatitis B reactivation receive anti-viral prophylaxis while receiving R-CHOP, but do not specify which drug should be used. At the recent annual meeting of the American Society of Clinical Oncology in Chicago, Dr. He Huang from Sun Yatsen University Cancer Center presented the results of a trial comparing two of the most commonly used drugs: entecavir and lamivudine.

Study subjects included patients receiving R-CHOP for previously untreated DLBCL and evidence of active infection (HBsAg-positive). Of the 121 HBsAg-positive patients, 61 were randomly assigned to entecavir and 60 to lamivudine. The primary endpoint was the incidence of HBV-related hepatitis; the secondary endpoint was chemotherapy disruption due to hepatitis.

The entecavir group had significantly lower rates of hepatitis, hepatitis B reactivation, and disruption of chemotherapy. The study concluded that for HBsAg-positive DLBCL patients receiving R-CHOP, entecavir was more effective in preventing hepatitis B reactivation, and should be considered the standard for primary preventive therapy in advanced stages of the disease.