Tag: ibrutinib

New Clinical Trials: Innovative Approaches for Follicular Lymphoma

The Weill Cornell Lymphoma Program has recently opened two clinical trials sponsored by The Alliance for Clinical Trials in Oncology. These trials are notable for their innovative approach. As Lymphoma Program Director and current chair of the committee, Dr. John Leonard explained, “Under the leadership of Bruce Cheson, MD, the lymphoma committee has been focused on ‘biologic doublets’ with targeted agents, a treatment approach that has been quite innovative. Following up on his work we are now moving toward ‘targeted triplet therapy’ which is a first in lymphoma therapeutics. These are important steps as we move such ‘chemotherapy-free’ approaches more and more into standard treatment.”

A051103 – A Phase I Study of Rituximab, Lenalidomide, and Ibrutinib in Previously Untreated Follicular Lymphoma

In the first trial, principal investigator, Dr. Peter Martin seeks to evaluate the effect of rituximab, lenalidomide, and ibrutinib in untreated follicular lymphoma. For more information about the untreated follicular lymphoma trial, please call Amelyn Rodriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility
  • Untreated Follicular Lymphoma
  • No prior systemic therapy for non-Hodgkin lymphoma
  • Detailed eligibility reviewed when you contact the study team

Study Details

The purpose of the study is to test the combination of the drugs lenalidomide and ibrutinib (also called PCI-32765) at different dose levels, in combination with the drug rituximab. The study is evaluating the side effects and best dose of lenalidomide and ibrutinib for combination with rituximab in previously untreated follicular lymphoma.

Treatment Plan

Over the course of  each 28 day treatment cycle patients will receive lenalidomide by mouth every day on Days 1 through 21, ibrutinib by mouth on Days 1 through 28 of each cycle, and rituximab via infusion on Days 1, 8, 15, & 22 of Cycle 1 and during the first week of Cycle 4 & 6 & 10. 

Different dosses of lenalidomide and ibrutinib will be tested in small groups of participants.

A051202 – A Phase I Trial of Lenalidomide, Rituximab, and Idelalisib in Recurrent Follicular Lymphoma

In the second trial, principal investigator, Dr. John Leonard seeks to evaluate the effect of lenalidomide, rituximab, and idelalisib in recurrent follicular lymphoma. For more information about the recurrent follicular lymphoma trial, please call Amelyn Rodriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility
  • Men and women age 18 and older
  • Previously treated follicular lymphoma
  • Must have had prior treatment with rituximab either alone or in combination with chemotherapy
  • Detailed eligibility reviewed when you contact the study team

Study Details

The purpose of the study is to test the combination of the drugs lenalidomide and idelalisib at different dose levels, in combination with the drug rituximab. The study is evaluating the side effects and best dose of lenalidomide when given with rituximab and idelalisib in people with recurrent follicular lymphoma. Rituximab is FDA-approved for use in follicular lymphoma, but lenalidomide and idelalisib are not FDA-approved for treating follicular lymphoma.

Treatment Plans

Treatment cycles are 21 days long. Participants will receive lenalidomide by mouth once a day on Days 1 through 21, followed by one week off, of each cycle for 12 cycles, idelalisib by mouth twice a day for 12 cycles, and rituximab via infusion during Cycle 1 on Day 15 & 22, and on Day 1 of Cycle 2 for a total of 4 infusions.

Click here to view all current lymphoma trials at Weill Cornell Medical College

Ibrutinib is Effective Therapy for Relapsed CLL Patients

Reporting results in the New England Journal of Medicine, Weill Cornell’s Dr. Richard Furman and others recently completed a large phase 1b/2 clinical trial on the effects of ibrutinib in patients with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL). Recently granted a third breakthrough therapy designation as a monotherapy for CLL and SLL, ibrutinib acts as an oral, irreversible inhibitor of the enzyme, Bruton tyrosine kinase (BTK).  BTK is an essential component of the B-cell receptor signaling pathway and  facilitates interactions between the CLL cells and their micro-environment, promoting the survival of CLL/SLL cells.

In the clinical study, ibrutinib was administered orally to 85 previously treated patients with CLL once daily at doses of 420 mg and 840 mg. Both doses demonstrated an overall response rate of 71%, with an additional 20% and 15% in each group achieving a partial response with lymphocytosis. At a median follow up of 26 months, estimated progression-free and overall survival for the 85 patients overall were 75% and 83% respectively. Side effects were mild and included diarrhea, fatigue, and infections. The study concluded that ibrutinib produces, “a high frequency of durable remissions for relapsed or refractory CLL/SLL, including those patients with high-risk genetic lesions.”

Ibrutinib represents an important improvement in the treatment of patients with CLL/SLL.  Treatment previously consisted of regimens utilizing chemotherapies, including chlorambucil, cyclophosphamide, fludarabine, and bendamustine in various combinations that effectively generated responses in patients, but with significant toxicities.  Ultimately, patients relapsed and became unresponsive to or unable to tolerate chemotherapy.  Additionally, the subset of patients characterized by having del 17p13.1  who respond extremely poorly to chemoimmunotherapy, demonstrated response rates equivalent to the rest of the patient population.

Currently there are ongoing trials of ibrutinib in CLL and other lymphomas at the Weill Cornell CLL Research Center and Lymphoma Program. Additional clinical trials are available here.

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.