The Genetics of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) in African Americans and Other Minorities
This content was current as of the date it was released. In science and medicine, information is constantly changing and may become out-of-date as new data emerge.
We received this announcement of three new clinical trials of interest for those of us with CLL.
Activating the immune system is a proven successful approach to controlling cancer such as the cures we have seen in CLL with allogeneic stem cell transplants. These trials are looking for the same success we see with a transplant without the downside risks.
These are investigator-initiated trials that mean that they are designed and managed by the investigator and not by the pharmaceutical company so they are often trying to answer different kinds of questions.
Please note that all three trials are chemo-free. See below the explanation by Dr. Nitin Jain.
Brian Koffman 10/26/15
At MD Anderson Cancer Center, we have initiated several clinical trials with antibodies that modulate the immune system. The basic premise of these trials is that the immune system of patients with CLL does not function properly, and therefore, activation of the immune system may lead to killing of CLL cells. These principles have already been successfully applied for patients with solid tumors.
For further information on any of the clinical trials listed below, please feel free to contact us directly:
Dr. Nitin Jain, njain@mdanderson.org, Office Phone: 713-745-6080
Dr. William Wierda, wwierda@mdanderson.org, Office phone: 713-745-0554
- Nivolumab (PD-1 mAb) in combination with Ibrutinib (NCT02420912)
Rationale for the trial: In a normal immune system, the function of T cells is to kill any thing that is foreign to the human body. This is the way we protect ourselves from getting viral infections etc.
In patients with CLL, these T cells are present but are ‘silent’. They do not kill the leukemia cells.
We now know that that this is in part due to expression of certain proteins on the surface of T cells (such as PD-1) and on the CLL cells (such as PD-L1). Blocking this interaction between PD-1 and PD-L1 by an antibody (such as nivolumab) leads to improvement in the function of the T cells (“takes the brakes off”), and these T cells can then kill the cancer cells. This has already been successfully used in solid tumors such as melanoma and lung cancer. Addition of ibrutinib to nivolumab has been shown to have synergistic efficacy in mouse models.
Trial Population: This trial has 2 cohorts:
Cohort 1 includes patients with who have received prior therapies or untreated patients with del(17p). Patients will start with nivolumab (given IV), and ibrutinib.
Cohort 2 includes patients who are already on ibrutinib and have achieved a partial response (i.e. more than 50% improvement but less than complete response). The goal for this group of patients is to add nivolumab as a ‘consolidation strategy’ to improve the partial response to complete response.
For more information: https://clinicaltrials.gov/ct2/show/NCT02420912
- Urelumab (CD137 mAb) in combination with Rituximab (NCT02420938)
Rationale for the trial: In a normal immune system, the function of T cells is to kill any thing that is foreign to the human body. This is the way we protect ourselves from getting viral infections etc.
In patients with CLL, these T cells are present but are ‘silent’. They do not kill the leukemia cells. Similarly, NK cells, another cell of the immune system, do not work properly in patients with CLL. This trial uses an antibody (CD137 antibody) that directly activates the T cells and NK cells. NK cells also help mediate activity of rituximab, and therefore, activated NK cells should lead to better efficacy of rituximab. Laboratory data suggest that combining CD137 antibody and rituximab is synergistic.
Trial Population: Patients with CLL who have received prior therapies for CLL
For more information: https://clinicaltrials.gov/ct2/show/NCT02420938
- Lirilumab (KIR mAb) in combination with Rituximab (NCT02481297)
Rationale for the trial: NK cells, a component of the immune system, do not work properly in patients with CLL. NK cells express a protein called KIR which suppresses the function of NK cells. Blocking this protein with an antibody will lead to activation of NK cell function. NK cells also help mediate activity of rituximab, and therefore, activated NK cells should lead to better efficacy of rituximab. Laboratory data suggest that combining KIR antibody (such as lirilumab) and rituximab is synergistic.
Trial Population: This trial has 2 cohorts
Cohort 1 includes patients with CLL who have received prior therapies for CLL.
Cohort 2 includes untreated patients with high-risk features such as deletion 17p, TP53 mutation, deletion 11q, unmutated IGHV, or age >65 year.
For more information: https://clinicaltrials.gov/ct2/show/NCT02481297
Dr. Nitin Jain 10/26/15
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