Rituxan/Bendamustine/PCI-32765 in Relapsed DLBCL, MCL, or Indolent Non-Hodgkin’s Lymphoma

This study is currently recruiting participants.
Verified June 2012 by Ohio State University Comprehensive Cancer Center

First Received on November 1, 2011.  
Last Updated on June 6, 2012  
History of Changes
This Clinical Trial Sponsored By: Kristie Blum
Collaborator: Pharmacyclics
Information provided by (Responsible Party): Kristie Blum, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01479842

Purpose for Clinical Trial

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 Study Intervention Clinical Trial 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: Study Interventional
Study Design: Endpoint Classification: Safety Study
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

Resource links provided by NLM:

Genetics Home Reference related topics:
MedlinePlus related topics:
Drug Information available for:
Bendamustine hydrochloride

U.S. FDA Resources

Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures For Clinical Trial:

  • 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 ] [ Designated as safety issue: Yes ]
    MTD is defined as the highest dose Level at which =< 1 of 6 patients experienced a DLT.

Secondary Outcome Measures For Clinical Trial:

  • Frequency, severity, and relatedness of adverse events [ Time Frame: up to 30 days after last dose of treatment ] [ Designated as safety issue: Yes ]
    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.

  • Overall response rate [ Time Frame: up to 24 months post treatment ] [ Designated as safety issue: No ]
    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 anaylsis.

  • Duration of response [ Time Frame: up to 24 months post treatment ] [ Designated as safety issue: No ]
    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.

  • Identification of germinal center versus nongerminal center DLCL [ Time Frame: screening or cycle 1 day 1 predose ] [ Designated as safety issue: No ]
    Determined by immunohistochemistry in patients with DLCL enrolled in the dose escalation portion of the study and in the DLCL expansion cohort.

  • Correlation of PGx with response and toxicity [ Time Frame: screening or cycle 1 day 1 predose ] [ Designated as safety issue: No ]
    Data will be evaluated with pharmacokinetics and clinical outcomes to identify significant associations and potential PGx biomarkers.

Estimated Enrollment: 48
Study Start Date: December 2011
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)


Assigned Study 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:
  • Bruton’s tyrosine kinase inhibitor PCI-32765
  • PCI-32765

Biological: rituximab

Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • Rituxan

Drug: bendamustine hydrochloride

Given IV
Other Names:
  • bendamustin hydrochloride
  • bendamustine
  • cytostasan hydrochloride
  • Treanda

Other: pharmacogenomic studies

Correlative studies
Other Name: Pharmacogenomic Study

Other: pharmacological study

Correlative studies
Other Name: pharmacological studies

Other: laborator

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