Btk Inhibitor in Recurrent B Cell Lymphoma
| Status: | Archived |
|---|---|
| Conditions: | Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | July 2010 |
| End Date: | July 2012 |
Phase 1 Dose-Escalation Study of Bruton's Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Recurrent B Cell Lymphoma
Background:
- PCI-32765 is a type of drug called a Bruton's Tyrosine Kinase (Btk) inhibitor, which
blocks a protein that is implicated in the development of B cell lymphoma. Laboratory tests
have shown that the drug can be used to treat lymphoma, and researchers are interested in
testing the drug on individuals who have B cell lymphoma that has not responded to standard
treatments.
Objectives:
- To determine the safety and the maximum tolerated dose of Btk inhibitor PCI-32765 in
patients with recurrent B cell lymphoma.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with B cell lymphoma that
has not responded to standard treatment.
- Individuals must not have had an allogeneic bone marrow transplant.
Design:
- Participants will be screened with a physical examination, medical history, blood and
urine tests, imaging studies, and an eye examination.
- Participants will receive PCI-32765 once a day for 35 days (5-week cycle). Participants
will keep a diary to record their response to treatment and any side effects.
- Participants will have study visits on days 1, 2, 8, 15, 22, and 29 of Cycle 1 and on
days 1 and 15 of cycles 2 and beyond. At these visits, blood samples will be taken and
other tests, including eye exams and imaging studies, may be performed. Participants
will provide blood samples on other days throughout the study as directed.
- Participants will continue to receive the study drug unless there are serious side
effects or the disease progresses.
- After the end of the study, participants will have study visits 1 month after the last
dose of the drug, and may need to have additional imaging studies as directed by the
study researchers.
Background:
- The role of Bruton's Tyrosine Kinase (Btk) in BCR signaling is well established by the
existence of the human genetic immunodeficiency disease X-linked agammaglobulinemia
(XLA), and the mouse genetic immunodeficiency disease X-linked immunodeficiency (xid),
both caused by a mutation in the Btk gene.
- The Btk protein is expressed in most hematopoietic cells with the exception of T cells
and natural killer (NK) cells, but the selective effect of Btk mutations suggests that
its primary functional role is in antigen receptor signaling in B cells.
- Recently reported findings indicate that BCR pathway components are frequently mutated
in the activated B cell (ABC) subtype of diffuse large B cell lymphoma (DLBCL) and Btk
knockdown selectively inhibits growth of ABC DLBCL tumor cell lines.
- Since preclinical data suggest that PCI-32765 (a Btk inhibitor) may be an active
anti-tumor agent, the tolerability, safety, and pharmacokinetics of this drug will be
investigated in a Phase I study in patients with recurrent B cell lymphoma for whom no
curative therapy is available.
Objectives:
- Establish the safety and the maximum tolerated dose (MTD) of orally administered
PCI-32765 in patients with recurrent B cell lymphoma.
- Determine pharmacokinetics (PK) of orally administered PCI-32765.
- Measure pharmacodynamic parameters to include drug occupancy of Btk, the target enzyme,
and effect on biological markers of B cell function.
Eligibility:
- For this site, must have non-GCB subtype of DLBCL by IHC.
- Women and men greater than or equal to 18 years of age, ECOG performance status of less
than or equal to 1.
- Have failed greater than or equal to 1 previous treatment for lymphoma and no standard
therapy is available. Patients with diffuse large B cell lymphoma must have failed,
refused or be ineligible for autologous stem cell transplant.
- Ability to swallow oral capsules without difficulty.
- No history of prior allogeneic bone marrow transplant.
- No immunotherapy, chemotherapy, radiotherapy or experimental therapy within 4 weeks
before first day of study drug dosing.
- No known human immunodeficiency virus (HIV) infection.
Study Design:
- Ten patients with pre-identified DLBCL ABC subtype lymphoma will be enrolled at the
NCI. Patients will receive a fixed dose of PCI-32765 at 560 mg (4 x 140-mg capsules)
once daily for 35 days without interruption. Each cycle is 35 days. There will be no
rest period between each cycle.
- In the continuous dosing cohort and the ABC DLBCL cohort, 35-day cycles can continue
without interruption until disease progression or the investigator no longer considers
the treatment tolerable.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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