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

NCT01479842 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-10052NCI-2011-03293
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue

Outcome Measures

Primary Outcomes (1)

• 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

  MTD is defined as the highest dose Level at which =\< 1 of 6 patients experienced a DLT.

  during first course of therapy

Secondary Outcomes (5)

• Frequency, severity, and relatedness of adverse events

  up to 30 days after last dose of treatment

• Overall response rate

  up to 24 months post treatment

• Duration of response

  up to 24 months post treatment

• Identification of germinal center versus nongerminal center DLCL

  screening or cycle 1 day 1 predose

• Correlation of PGx with response and toxicity

  screening or cycle 1 day 1 predose

Study Arms (1)

Treatment (enzyme inhibitor, chemo, monoclonal antibody)

EXPERIMENTAL

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; Biological: rituximab; Drug: bendamustine hydrochloride; Other: pharmacogenomic studies; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Treatment (enzyme inhibitor, chemo, monoclonal antibody)

bendamustine hydrochloride DRUG

Given IV

Also known as: bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Treanda

Treatment (enzyme inhibitor, chemo, monoclonal antibody)

pharmacogenomic studies OTHER

Correlative studies

Also known as: Pharmacogenomic Study

Treatment (enzyme inhibitor, chemo, monoclonal antibody)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (enzyme inhibitor, chemo, monoclonal antibody)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzyme inhibitor, chemo, monoclonal antibody)

BTK inhibitor PCI-32765 DRUG

Given PO

Also known as: Bruton's tyrosine kinase inhibitor PCI-32765, PCI-32765

Treatment (enzyme inhibitor, chemo, monoclonal antibody)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Kami Maddocks, MD: lead
• Pharmacyclics LLC.: collaborator

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• Maddocks K, Christian B, Jaglowski S, Flynn J, Jones JA, Porcu P, Wei L, Jenkins C, Lozanski G, Byrd JC, Blum KA. A phase 1/1b study of rituximab, bendamustine, and ibrutinib in patients with untreated and relapsed/refractory non-Hodgkin lymphoma. Blood. 2015 Jan 8;125(2):242-8. doi: 10.1182/blood-2014-08-597914. Epub 2014 Oct 29.

  PMID: 25355819 RESULT

Related Links

• Jamesline

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia

Interventions

ibrutinib; Rituximab; Bendamustine Hydrochloride; Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Kami Maddocks, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 1, 2011
• First Posted: November 28, 2011
• Study Start: March 26, 2014
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)