Treatment of Chronic Lymphocytic Leukemia

Leukemia, Lymphocytic, Chronic, B-Cell Clinical Trial

Official title:

Resistances of CLL and Treatment of CLL

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02757586
• Other study ID #: Study on CLL
• Status: Not yet recruiting
• Phase: N/A
• First received: April 17, 2016
• Last updated: May 11, 2016
• Start date: December 2016
• Est. completion date: December 2019

Study information

• Verified date: May 2016
• Source: Peking University People's Hospital
• Contact: Xiao-Hui Zhang, Doctor
• Phone: 861088324577
• Email: zhangxh100[@]sina.com
• Is FDA regulated: No
• Health authority: China: National Health and Family Planning Commission
• Study type: Observational

Clinical Trial Summary

CLL is a disease of the elderly, identifying effective therapies with better toxicity profiles is thus a high priority, and targeted therapies may allow attainment of this goal.

Description:

Chronic lymphocytic leukemia (CLL) is a common adult leukemia characterized by the extensive accumulation of monoclonal, relatively mature CD5+CD23+ B lymphocytes in lymphoid organs, bone marrow, and peripheral blood. CLL cells accumulate because of defective apoptosis, which extends survival. CLL is a heterogeneous disease. Chemoimmunotherapy is the standard front-line approach for patients younger than 65 years with CLL, with the combination of fludarabine, cyclophosphamide, and rituximab used most commonly. Some CLL patients do not respond well to routine chemoimmunotherapy. Despite recent advances in the treatment of CLL by use of modern chemoimmunotherapy, the disease remains incurable for most patients with the exception of those who have the option of an allogeneic transplantation. However, treatments with chemoimmunotherapy are associated with significant toxicities and sustained immunosuppression, and the rates of myelosuppression and infection are high. Such complications are more frequent and more severe in patients older than 65 years because of reduced marrow reserve, and presence of comorbidities. Because CLL is a disease of the elderly, identifying effective therapies with better toxicity profiles is thus a high priority, and targeted therapies may allow attainment of this goal.

CLL tumor cells are highly dependent on the microenvironment where cytokines (eg, CD40L, BAFF, IL-4, IL-6), and contact (eg, stromal cells) promote cell activation and proliferation, and also resistance to spontaneous and drug-mediated apoptosis. Many of these microenvironment-activated pathways merge with TSPs exported by XPO1. XPO1 is therefore a highly attractive molecular target to explore in CLL, because it impacts multiple antitumor and growth suppressive signaling pathways that are dysregulated in this disease.

The investigators therefore hypothesized that a selective XPO1 inhibitor would show efficacy with an acceptable therapeutic index in CLL and other diseases. Indeed, XPO1 inhibition in normal cells (ie, possessing an intact genome) leads to transient cell cycle arrest without cytotoxicity, followed by fast recovery after the drug is removed. To date, efforts to clinically pharmacologically inhibit XPO1 have been unsuccessful because of off-target effects. A selective XPO1 antagonist may allow targeting of the TSPs axes in tumor cells.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 70
• Est. completion date: December 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• patients with CLL

Study Design

Observational Model: Case-Crossover, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Genetic:
• shRNA
Using shRNA interfered the expression of the gene of CLL

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Peking University People's Hospital	Beijing Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall response		2 years	No