PCI-32765 for Special Cases of Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
- Chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) are types of blood or lymph node cancers that mostly affect the elderly. CLL/SLL both create abnormal white blood cells that hurt the immune system and make it more difficult to fight infections. These cancers are usually diagnosed after age 50; more than half of the people with CLL/SLL are over age 70. Elderly people often do not respond well to standard chemotherapy for CLL/SLL. They may have other health problems that make chemotherapy difficult. In addition, individuals who have a genetic abnormality called 17p deletion also do not respond well to standard treatments for CLL/SLL. Researchers want to test a new cancer treatment drug, PCI-32765, to see if it can treat CLL/SLL in these hard-to-treat groups.
- To see if PCI-32765 is a safe and effective treatment for CLL/SLL in older people and people with 17p deletion.
- Individuals over 65 years of age who have CLL/SLL.
- Individuals at least 18 years of age who have CLL/SLL and 17p deletion.
- Participants will be screened with a medical history, physical exam, and imaging studies. Blood and urine samples will be taken. Optional bone marrow and lymph node biopsies may also be taken.
- Participants will take PCI-32765 capsules every day for 28 days (one cycle of treatment). Treatment will be monitored with frequent blood tests and clinic visits.
- PCI-32765 will be given for six cycles of treatment. Those who benefit from the drug will continue to take it as long as there are no side effects and the disease does not progress. Those who do not benefit will stop treatment and have regular followup exams.
CLL (Chronic Lymphocytic Leukemia)
SLL (Small Lymphocytic Lymphoma)
Drug: PCI 32765
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of PCI-32765 for Patients With Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Need Therapy and Are Older Than 65 or Have a 17p Deletion|
- Determine the overall response rate (ORR) of PCI 32765 at 420 mg in CLL/ SLL after 6 cycles. [ Time Frame: 1 year ]
- Safety and tolerability of PCI 32765 [ Time Frame: 1 year ]
- Overall survival (OS) [ Time Frame: 1 year ]
- Progression free survival (PFS) [ Time Frame: 1 year ]
- Effect of PCI 32765 on tumor biology [ Time Frame: 1 year ]
- Pharmacokinetics and pharmacodynamics (target inhibition) in blood, bone marrow, and lymph node
|Study Start Date:||November 2011|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
|Experimental: Elderly greater than 65||
Drug: PCI 32765
420 mg daily
|Experimental: 17p Deletioin||
Drug: PCI 32765
420 mg daily
CLL/SLL is a malignancy of B cells that predominantly affects the elderly population. Diagnosis is typically made in adults over the age of 50 and more than half of the people with CLL/SLL are over the age of 70. Elderly patients in particular have other comorbidities that limit the tolerability of standard CLL/SLL chemoimmunotherapy regimens and they often have inferior response to these particular regimens. In addition, those patients with a 17p deletion also have inferior outcomes due to rapid progression of disease as well as refractoriness to standard treatment regimens.
It is still unclear what leads to the development of CLL/SLL. However, recent studies indicated that B cell receptor (BCR) signaling is an important contributor to the disease and could be a target for therapy. Bruton s Tyrosine Kinase (Btk) is an enzyme required for BCR signaling.
PCI-32765 is a potent and selective inhibitor of Bruton Tyrosine Kinase (Btk). In vitro lymphoma models have demonstrated that PCI-32765 inhibits Btk. Inhibition of Btk blocks downstream BCR signaling pathways and thus prevents B cell proliferation. A phase 1 study of PCI-32765 shows activity in multiple lymphomas including CLL/SLL.
This study will investigate the efficacy of PCI-32765 for patients with CLL/SLL in patients that are older than 65 who are in need of therapy. In addition, those patients with a 17p deletion will also be treated as an early intervention as overall survival is poor in this patient cohort. This protocol is intended both for patients who have been untreated and those who have undergone other therapies.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Mohammed Z Farooqui, D.O.||National Heart, Lung, and Blood Institute (NHLBI)|