- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01479842
Rituxan/Bendamustine/PCI-32765 in Relapsed DLBCL, MCL, or Indolent Non-Hodgkin's Lymphoma
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
Study Overview
Status
Conditions
- 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
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Ohio
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Columbus, Ohio, United States, 43210
- Ohio State University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
- Patients with DLCL must be relapsed or refractory after previous autologous stem cell transplant unless transplant is contraindicated
- Patients with MCL, follicular lymphoma (FL), marginal zone lymphoma, or Waldenstrom's macroglobulinemia are eligible after >= 1 prior therapies; however, patients with MCL who are not eligible for stem cell transplant (due to age or other co-morbidities) or refuse up-front stem cell transplantation may receive study treatment as their first-line therapy
- Body weight >= 40 kg
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- Agreement to use contraception during the study and for 30 days after the last dose of study drug if sexually active and able to bear children
- Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations)
Exclusion Criteria:
- Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient has been disease free for at least 2 years or which will not limit survival to < 2 years (Note: these cases must be discussed with the Principal Investigator)
- A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk
- Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
- Any immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 3 weeks before first dose of study drug (corticosteroids for disease-related symptoms allowed but require 1-week washout before study drug administration)
- Use of medications known to prolong QTc interval or that may be associated with Torsades de Pointes are prohibited within 7 days of starting study drug and during treatment
- Central nervous system (CNS) involvement by lymphoma
- Grade >= 2 toxicity (other than alopecia) related to prior anticancer therapy including radiation
- Known history of human immunodeficiency virus (HIV), active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV surface antigen positive), carriers of HBV (surface antigen and surface antibody negative, but HBV core antibody positive), or any uncontrolled active systemic infection
- Major surgery within 4 weeks before first dose of study drug
- Previous serious infusion reactions or hypersensitivity to rituximab or bendamustine not controlled or prevented by steroid pre-medication
- Creatinine > 2.0 mg/dL
- Total bilirubin > 1.5 x upper limit of normal (ULN) (unless due to Gilbert's disease)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
- Absolute neutrophil count (ANC) < 1000/mm^3
- Platelets < 50,000/mm^3
- Lactating or pregnant
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
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Correlative studies
Given IV
Other Names:
Correlative studies
Other Names:
Given IV
Other Names:
Correlative studies
Other Names:
Given PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose (MTD) as determined by the incidence of dose limiting toxicities (DLT) of BTK inhibitor PCI-32765 when given in combination with rituximab and bendamustine hydrochloride
Time Frame: during first course of therapy
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MTD is defined as the highest dose Level at which =< 1 of 6 patients experienced a DLT.
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during first course of therapy
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Frequency, severity, and relatedness of adverse events
Time Frame: up to 30 days after last dose of treatment
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Laboratory shift tables containing counts and percentages will be prepared by treatment assignment, laboratory parameter, and time.
Summary tables will be prepared for each laboratory parameter.
Figures of changes in laboratory parameters over time will be generated.
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up to 30 days after last dose of treatment
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Overall response rate
Time Frame: up to 24 months post treatment
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The point estimate of the rate will be calculated for the per protocol analysis set.
The response rate 95% confidence interval estimates also will be derived.
Association between the correlation markers and response will be explored using graphical and descriptive analysis.
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up to 24 months post treatment
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Duration of response
Time Frame: up to 24 months post treatment
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From time measurement criteria are met for complete response(CR)or partial response(PR)until the first date that recurrent or progressive disease occurs.
Median duration of overall response will be assessed with 95% confidence interval.
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up to 24 months post treatment
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Identification of germinal center versus nongerminal center DLCL
Time Frame: screening or cycle 1 day 1 predose
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Determined by immunohistochemistry in patients with DLCL enrolled in the dose escalation portion of the study and in the DLCL expansion cohort.
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screening or cycle 1 day 1 predose
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Correlation of PGx with response and toxicity
Time Frame: screening or cycle 1 day 1 predose
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Data will be evaluated with pharmacokinetics and clinical outcomes to identify significant associations and potential PGx biomarkers.
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screening or cycle 1 day 1 predose
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Kami Maddocks, MD, Ohio State University
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Neoplasms, Plasma Cell
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Recurrence
- Lymphoma, Non-Hodgkin
- Lymphoma, Mantle-Cell
- Lymphoma, B-Cell, Marginal Zone
- Waldenstrom Macroglobulinemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Bendamustine Hydrochloride
- Rituximab
- Tyrosine Protein Kinase Inhibitors
Other Study ID Numbers
- OSU-10052
- NCI-2011-03293 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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