Recruitment

Recruitment Status
Active, not recruiting

Inclusion Criteria

Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
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)
...
Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
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)
Patients with DLCL must be relapsed or refractory after previous autologous stem cell transplant unless transplant is contraindicated
Body weight >= 40 kg
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
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

Exclusion Criteria

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
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)
Creatinine > 2.0 mg/dL
...
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
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)
Creatinine > 2.0 mg/dL
Grade >= 2 toxicity (other than alopecia) related to prior anticancer therapy including radiation
Previous serious infusion reactions or hypersensitivity to rituximab or bendamustine not controlled or prevented by steroid pre-medication
Total bilirubin > 1.5 x upper limit of normal (ULN) (unless due to Gilbert's disease)
Lactating or pregnant
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
Absolute neutrophil count (ANC) < 1000/mm^3
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
Platelets < 50,000/mm^3
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
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
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
Major surgery within 4 weeks before first dose of study drug
Central nervous system (CNS) involvement by lymphoma
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)

Summary

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
Type
Interventional
Phase
Phase 1
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

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. SEC...

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.

Inclusion Criteria

Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
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)
...
Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
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)
Patients with DLCL must be relapsed or refractory after previous autologous stem cell transplant unless transplant is contraindicated
Body weight >= 40 kg
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
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

Exclusion Criteria

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
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)
Creatinine > 2.0 mg/dL
...
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
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)
Creatinine > 2.0 mg/dL
Grade >= 2 toxicity (other than alopecia) related to prior anticancer therapy including radiation
Previous serious infusion reactions or hypersensitivity to rituximab or bendamustine not controlled or prevented by steroid pre-medication
Total bilirubin > 1.5 x upper limit of normal (ULN) (unless due to Gilbert's disease)
Lactating or pregnant
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
Absolute neutrophil count (ANC) < 1000/mm^3
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
Platelets < 50,000/mm^3
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
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
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
Major surgery within 4 weeks before first dose of study drug
Central nervous system (CNS) involvement by lymphoma
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)

Tracking Information

NCT #
NCT01479842
Collaborators
Pharmacyclics LLC.
Investigators
  • Principal Investigator: Kami Maddocks, MD Ohio State University
  • Kami Maddocks, MD Ohio State University