A Phase II Study Using Ibrutinib and Short-Course Fludarabine in Previously Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
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|ClinicalTrials.gov Identifier: NCT02514083|
Recruitment Status : Recruiting
First Posted : August 3, 2015
Last Update Posted : May 23, 2019
- Chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma (SLL) are tumors of abnormal B cells that often affect elderly patients. Studies have identified critical factors required for the growth of CLL cells. First, CLL cells survive because they receive signals through the B-cell receptor. Second, CLL cells benefit from interactions with other cells, especially T cells.
- Survival signals through the B-cell receptor can be reduced with ibrutinib, which is a pill taken daily by mouth. Ibrutinib has been approved by the U.S. Food and Drug Administration to treat CLL patients.
- T cells that interact with CLL cells can be removed by fludarabine, which is a drug given by vein and has been widely used to treat CLL. By adding a short course of fludarabine, we hope to complement the action of ibrutinib and restore a healthier immune system.
- To determine if ibrutinib and a short course of fludarabine can be used safely and effectively to treat CLL or SLL.
- Diagnosed with CLL or SLL requiring treatment
- No prior treatment for CLL or SLL
- Age greater than or equal to 18 years
- Not pregnant or breast-feeding women
- Adequate kidney and liver function
- This is a phase II study of 32 patients.
- Participants will be screened with blood tests and physical exam for eligibility.
Eligible participants will be treated with ibrutinib and a short course of fludarabine;
- Treatment is given in cycles. Each cycle is defined as 28 days. Treatment continues as long as it is effective and safe for participants.
- Ibrutinib is taken by mouth starting on the first day of cycle 1. Ibrutinib is continued daily.
- Fludarabine is given through vein on the first five days of cycle 3 and 4 only. Each infusion takes approximately 30 minutes.
- Participants will also take drugs that prevent infections and other complications.
Participants under treatment will have clinic visits with tests including:
- Medical history
- Physical exam
- Blood and urine tests
- CT and PET scans: They will lie in a machine that uses a computer to take serial images of the body.
- For the PET scan, a radioactive sugar is injected into a vein for clear visualization of the body.
- EKG: To assess heart rhythm.
- Bone marrow and lymph node biopsies
- Participants should avoid grapefruit, Seville oranges, and grapefruit juice during the study. They also should avoid any live vaccines.
|Condition or disease||Intervention/treatment||Phase|
|Hematopoietic Neoplasms Tumors of B Cells B-cell Surface Antigens CD19, CD20 and CD23 T-cell Antigen CD5 B-cell Receptor (BCR)||Drug: Ibrutinib Drug: Fludarabine||Phase 2|
Chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma (SLL) are tumors of B cells that often affect elderly patients. While the cause of CLL is still unclear, studies have indicated critical factors required for the tumor cells. First, CLL cells grow and survive because they receive signals through the B-cell receptor (BCR); and second, CLL cells benefit from interactions with other cells, especially T cells.
The stimulation through the BCR can be reduced with ibrutinib, which is an oral drug that selectively inhibits Bruton s tyrosine kinase (BTK). In clinical trials, ibrutinib demonstrated safety and high response rates in patients with high-risk disease. Ibrutinib has gained FDA approval as a treatment for CLL patients with 17p deletion and for those who had at least one prior therapy. However, single-agent ibrutinib has limitations; the drug does not eliminate all the tumor cells, and, with time, the tumor cells may become resistant. Therefore, combination of ibrutinib with other drugs could be beneficial. Here we chose fludarabine because it is a well-tolerated drug that has been used widely to treat CLL. Also, fludarabine can kill both malignant B cells and T cells that support the growth of leukemia cells. With this approach we hope to restore healthier immune system.
This study will investigate the safety and efficacy of ibrutinib combined with fludarabine. This protocol is intended for previously untreated CLL patients. Ibrutinib will be given daily until disease progression or intolerable side effects occur. Fludarabine will be given only in cycles 3 and 4.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Phase II Study Using Ibrutinib and Short-Course Fludarabine in Previously Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)|
|Actual Study Start Date :||December 9, 2015|
|Estimated Primary Completion Date :||February 4, 2021|
|Estimated Study Completion Date :||July 1, 2021|
- Safety and efficacy of ibrutinib-based therapy combined with a short-course fludarabine in previously untreated patients with chronic lymphocytic leukemia (CLL) and/or small lymphocytic leukemia (SLL) [ Time Frame: 2 yrs ]Primary efficacy endpoint is the rate of complete response at 24 weeks or after 6 cycles. Primary safety endpoint is the rate of treatment discontinuation within the first 24 weeks or 6 cycles due to intolerable side effects.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02514083
|Contact: Inhye Ahn, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Inhye Ahn, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|