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| Sponsor: | Ohio State University Comprehensive Cancer Center |
|---|---|
| Collaborator: |
Pharmacyclics |
| Information provided by (Responsible Party): | Ohio State University Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01479842 |
Purpose
This phase I trial studies the side effects and best dose of BTK inhibitor PCI-32765 when given together with rituximab and bendamustine hydrochloride in treating patients with recurrent non-Hodgkin lymphoma (NHL). BTK inhibitor PCI-32765 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving BTK inhibitor PCI-32765 together with rituximab and bendamustine hydrochloride may kill more cancer cells.
| Condition | Intervention | Phase |
|---|---|---|
|
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Nodal Marginal Zone B-cell Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Splenic Marginal Zone Lymphoma Waldenstrom Macroglobulinemia |
Drug: BTK inhibitor PCI-32765 Biological: rituximab Drug: bendamustine hydrochloride Other: pharmacogenomic studies Other: pharmacological study Other: laboratory biomarker analysis |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I, Dose-escalation Trial of Rituxan and Bendamustine in Combination With Bruton's Tyrosine Kinase Inhibitor, PCI-32765, in Patients With Relapsed Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Indolent Non-Hodgkin's Lymphoma |
| Estimated Enrollment: | 48 |
| Study Start Date: | December 2011 |
| Estimated Primary Completion Date: | October 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (enzyme inhibitor, chemo, monoclonal antibody)
Patients receive BTK inhibitor PCI-32765 PO QD on days 1-28. Patients also receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue receiving BTK inhibitor PCI-32765 PO in the absence of disease progression or unacceptable toxicity.
|
Drug: BTK inhibitor PCI-32765
Given PO
Other Names:
Biological: rituximab
Given IV
Other Names:
Drug: bendamustine hydrochloride
Given IV
Other Names:
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
|
PRIMARY OBJECTIVES:
I. Identify the specific toxicities and a recommended phase 2 dose of PCI-32765 (BTK inhibitor PCI-32765) orally (PO) in combination with rituximab and bendamustine (bendamustine hydrochloride) (i.e., "combination therapy") in patients with relapsed and refractory B-cell NHL.
SECONDARY OBJECTIVES:
I. Evaluate the activity of combined rituximab, bendamustine, and PCI-32765 in patients with relapsed and refractory B-cell NHL as measured by response rate and duration of response.
II. Identify potential marker(s) predictive of response to the combination therapy.
III. Correlate pharmacogenetic (PGx) findings with patient response and toxicity.
OUTLINE: This is a dose-escalation study of BTK inhibitor PCI-32765.
Patients receive BTK inhibitor PCI-32765 PO once daily (QD) on days 1-28. Patients also receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients may continue receiving BTK inhibitor PCI-32765 PO in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 4 months for up to 2 years.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Histologically confirmed B-cell NHL of the following subtypes: follicular, marginal zone (nodal, splenic, or extranodal), Waldenstrom's macroglobulinemia, diffuse large B-cell (DLCL) or mantle cell lymphoma (MCL) according to 2008 World Health Organization (WHO) criteria that is relapsed or refractory after at least 1 prior therapy
Exclusion Criteria:
Contacts and Locations| Contact: Ohio State University Compreshensive Cancer Center | 1-800-293-5066 | jamesline@osumc.edu |
| Contact: Kristie Blum, MD | 614-293-4590 | Kristie.Blum@osumc.edu |
| United States, Ohio | |
| Ohio State University Medical Center | Recruiting |
| Columbus, Ohio, United States, 43210 | |
| Contact: Kristie A. Blum 614-293-4590 Kristie.Blum@osumc.edu | |
| Principal Investigator: Kristie A. Blum | |
| Principal Investigator: | Kristie Blum, MD | Ohio State University |
More Information
| Responsible Party: | Ohio State University Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01479842 History of Changes |
| Other Study ID Numbers: | OSU-10052, NCI-2011-03293 |
| Study First Received: | November 1, 2011 |
| Last Updated: | January 30, 2012 |
| Health Authority: | United States: Food and Drug Administration |
|
Lymphoma Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Waldenstrom Macroglobulinemia Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Mantle-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Neoplasms, Plasma Cell |
Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Antibodies Antibodies, Monoclonal Rituximab Bendamustine Nitrogen Mustard Compounds Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |