Tag: cancer clinical trials

Clinical Trial Participation May Improve Outcomes for Patients with Lymphoma

Picture1By Peter Martin, M.D.

Recently researchers from the Mayo Clinic presented data at the 2016 ASCO annual meeting suggesting that clinical trial participation might be associated with a survival benefit. The researchers used the Mayo Clinic Lymphoma Database to identify patients with relapsed Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), or relapsed mantle cell lymphoma (MCL), and compared the characteristics and outcomes of those enrolled in clinical trials versus those who were eligible, but not enrolled in clinical trials. Between January 2001 and December 2014, 340 patients with DLBCL, 159 with MCL, and 115 patients with HL were identified. Over this same period 47 unique Phase 1-3 trials led to the FDA approval of 17 treatments.

94 of 340 (27%) DLBCL, 63 of 159 (41%) MCL and 66 of 115 (57%) HL patients were enrolled on a clinical trial at some point during therapy, with 38% of patients enrolled in more than 1 study. Researchers found that the median survival of patients treated in a clinical trial was roughly twice as long as patients not treated on a clinical trial in all 3 lymphoma subtypes. There are several possible sources of bias or confounding that might explain the difference, despite the researchers’ efforts to control for these variables. Clearly, more research in this areas is indicated. Nonetheless, the magnitude of benefit was striking and should be reassuring to patients considering clinical trial participation.

New Clinical Trial: A Phase 1/2 Study to Assess the Safety & Tolerability of Durvalumab as Monotherapy & in Combination Therapy in Subjects with Lymphoma or CLL

The Weill Cornell Medicine Lymphoma Program has recently opened a new clinical trial for men and women with relapsed/refractory lymphoma or relapsed/refractory chronic lymphocytic leukemia (CLL). The study sponsor is Celgene International, and the principal investigator at Weill Cornell is Jia Ruan, M.D., Ph.D. For more information about the study, please call Catherine Babaran, RN at 212-746-2651 or e-mail Catherine at cmb9017@med.cornell.edu.

Key Eligibility

  • Men and women age 18 years and older.
  • Patients with relapsed/refractory lymphoma or relapsed/refractory CLL previously treated with at least one systemic therapy.
  • Detailed eligibility reviewed when you contact the study team.

Study Summary

This clinical trial is for men and women with relapsed/refractory lymphoma or relapsed/refractory chronic lymphocytic leukemia (CLL) previously treated with at least one systemic therapy.

The purpose of this study is to test the safety and effectiveness, as well as to define the appropriate dose and schedule of an investigational drug and investigational combinations of drugs. Durvalumab is an antibody (a protein that works with your immune system) that attaches to a molecule known as “programmed-cell-death ligand 1” (PD-L1). Signals from PD-L1 help cancers avoid detection by the immune system. Durvalumab blocks these signals, interfering with the cancer’s ability to escape the immune system.

The study will consist of 3 parts: dose findings, dose confirmation, and dose expansion. Four treatment arms will be investigated:

  • Arm A (durvalumab plus lenalidomide and ritxuimab)
  • Arm B (durvalumab plus ibrutinib)
  • Arm C (durvalumab plus bendamustine and rituximab)
  • Arm D (durvalumab monotherapy)

Study subjects will receive treatment for approximately one year and be in follow-up for anywhere from two to five years after treatment.

During each 28-day treatment cycle, subjects will receive durvalumab infusion on Day 1 of Cycles 1 through 13 at a fixed dose of 1500 mg every 4 weeks in combination with:

  • Arm A: Lenalidomide orally once daily on Days 1 to 21 of each cycle for 12 months or until disease progression plus rituximab infusion on Days 2, 8, 15 and 22 of Cycle 1 and on Day 1 of Cycles 2 through 5.
  • Arm B: Ibrutinib continuous, once daily until disease progression.
  • Arm C: Bendamustine infusion on Days 1 and 2 of Cycles 1 through 6 plus rituximab infusion on Day 2 of Cycles 1 through 6.
  • Arm D: Durvalumab monotherapy arm.

The FDA Breakthrough Therapy Designation: A Primer

 

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By Peter Martin, M.D.

The Breakthrough Therapy Designation was introduced as part of the 2012 Food and Drug Administration Safety and Innovation Act and is designed to expedite the development of new treatments for serious conditions like lymphoma. If preliminary evidence from clinical trials demonstrates that a new drug represents a significant improvement over currently available therapies, the drug developer (also called the Sponsor) may request a Breakthrough Therapy Designation.

If the FDA agrees with the Sponsor and grants the designation, they will subsequently commit to providing additional resources to the development and review process.  Practically this means  more frequent meetings and communications with senior FDA officials, and aid in designing more efficient clinical trials. Although the Breakthrough Therapy Designation does not make a new drug available, early experience with the program suggests that it can shave years off of the typical development process.

Since 2012, the Sponsors of 342 treatments have applied for this status, with 111 receiving the designation. Of the treatments that have received the designation 42 have received full approval. In 2016 pembrolizumab received the designation for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma and venetoclax received it in combination with rituximab to treat patients with relapsed/refractory chronic lymphocytic leukemia. Previously nivolumab, idelalisib, ofatumumab, obintuzumab, and ibrutinib all received the Breakthrough Therapy Designation for different lymphoma indications.

Despite the success of the program there are several points to keep in mind. The FDA’s definition of “breakthrough” is very different from its interpretation by lay persons and the media. The FDA’s definition refers to a drug that in the early stages of development has shown the potential for an improvement in patient care. It is not a guarantee of the approval or long-term success of the treatment.

As the FDA and Sponsors gain additional experience with the program we are likely to see some changes, including the number of applications and the cost of requesting a Breakthrough Therapy Designation. We are also likely to witness some unintended consequences, including investments by venture capitalists and opaque marketing strategies. When in doubt a patient should consult a physician about the usefulness of any treatment.

At the Weill Cornell Lymphoma Program, we are interested in any program that helps make promising new therapies available to patients as quickly as possible, and so we continue to follow this and other related programs closely. In the next post in the series we will discuss the Fast Track Designation.

Previous Entries in the Primer Series

The FDA Approval Process