Recruitment

Recruitment Status
Active, not recruiting
Estimated Enrollment
40

Inclusion Criteria

Willingness to provide biologic samples for correlative research purposes
Measurable disease as defined by a lymph node or tumor mass that is >= 1.5 cm in at least one dimension by CT or the CT portion of the PET/CT
Absolute neutrophil count >= 750/mm^3 (0.75 x 10^9/L)
...
Willingness to provide biologic samples for correlative research purposes
Measurable disease as defined by a lymph node or tumor mass that is >= 1.5 cm in at least one dimension by CT or the CT portion of the PET/CT
Absolute neutrophil count >= 750/mm^3 (0.75 x 10^9/L)
Negative serum pregnancy test done =< 7 days prior to registration for women of childbearing potential only
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) unless Gilbert's syndrome or disease infiltration of the liver is present
Relapsed or refractory follicular lymphoma which has progressed during or following 1 or more prior chemotherapy regimens for lymphoma
Note: Fresh (frozen) tumor biopsy must be available or attempted; a frozen tumor biopsy equivalent to a minimum of four at least 16 gauge needle cores is an important component of this study; patients without adequate frozen material should have a biopsy performed to obtain material; if biopsy is performed and does not yield adequate material, the patient is still eligible for the study; if a biopsy cannot be done safely, the patient may still be eligible for the study if permission is granted in writing (email) by the study chair (Dr. Nancy Bartlett) or her designees; Dr. Bartlett may be consulted to discuss situations involving invasive biopsy procedures that may pose an increased risk to the patient
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
Platelets >= 30,000/mm^3 (30 x 10^9/L)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x institutional ULN
Creatinine =< 2.0 x institutional ULN
Creatinine clearance (estimated [est.] glomerular filtration rate [GFR] Cockcroft-Gault) >= 30 mL/min
Ability to understand and the willingness to sign a written informed consent document
Hemoglobin >= 8.0 g/dL

Exclusion Criteria

Note: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ibrutinib administration
Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450 family 3 subfamily A member 4/5 (CYP3A4/5)
...
Note: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ibrutinib administration
Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450 family 3 subfamily A member 4/5 (CYP3A4/5)
Concurrent treatment with therapeutic doses (> 20 mg prednisone or equivalent) of systemic steroids within 14 days of start of protocol therapy
Nursing women
Receiving any other investigational agents
Prior history of allogeneic stem cell transplant
Note: HIV-positive patients who are not on anti-viral medications that are strong CYP3A4/5 inhibitors and who do not have cluster of differentiation (CD)4 counts less than the lower limit of normal by institutional criteria are eligible; no patients with CD4 counts below institutional normals are eligible
Note: Breastfeeding should be discontinued if the mother is treated with ibrutinib
Cardiac disease
Psychiatric illness/social situations that would limit compliance with study requirements
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib
Pregnant women
Uncontrolled diabetes mellitus
Active central nervous system (CNS) involvement
Radiotherapy =< 4 weeks prior to registration
Known active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
Major surgery =< 10 days prior to registration or minor surgery =< 7 days prior to registration
Note: Patients are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy, and are considered by their physician to be at less than 30% risk of relapse
Ongoing or active infection,
Prior therapy with ibrutinib or another Bruton's tyrosine kinase inhibitor
Chemotherapy/systemic therapy =< 4 weeks prior to registration
History of stroke or intracranial hemorrhage =< 6 months prior to the first dose of study drug
Patient has the inability to swallow tablets
Nitrosoureas or mitomycin C =< 6 weeks prior to registration
Note: Warfarin or similar vitamin K antagonist must have been discontinued at least 28 days prior to study entry
Note: A prior history of adequately treated transformed lymphoma does not exclude a patient if the current active disease is biopsy-proven follicular lymphoma

Summary

Conditions
  • Grade 3a Follicular Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Refractory Follicular Lymphoma
Type
Interventional
Phase
Phase 2
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. Evaluate the overall response rate of ibrutinib in patients with relapsed or refractory follicular lymphoma. SECONDARY OBJECTIVES: I. Assess the safety and tolerability of ibrutinib in patients with follicular lymphoma. II. Evaluate overall survival, time to response, duration...

PRIMARY OBJECTIVES: I. Evaluate the overall response rate of ibrutinib in patients with relapsed or refractory follicular lymphoma. SECONDARY OBJECTIVES: I. Assess the safety and tolerability of ibrutinib in patients with follicular lymphoma. II. Evaluate overall survival, time to response, duration of response, progression-free survival, time to treatment failure, and time to subsequent treatment. TERTIARY OBJECTIVES: I. Describe the relationship between interim positron emission tomography (PET)/computed tomography (CT) scan results, CT response, and response duration. II. Biomarker studies including exploring associations between ibrutinib response and somatic mutations identified in follicular lymphoma, whole transcriptome shotgun sequencing (ribonucleic acid-sequencing [RNA-seq]), exploration of inhibition of Bruton's tyrosine kinase (BTK) and other kinases, expression of cytokines, chemokines, and other proteins with an aim to develop predictors of response and resistance. III. Assess changes in various cancer-derived molecules in the blood over the course of treatment with ibrutinib. IV. As part of ongoing research for Phase II Consortium (P2C) studies, we are banking paraffin-embedded tissue blocks/slides and blood products for future studies. OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease at the end of course 2 may continue on therapy until the end of course 5 at the discretion of the treating physician. After completion of study treatment, patients are followed up every 3 months until progressive disease, and then every 6 months for 5 years.

Inclusion Criteria

Willingness to provide biologic samples for correlative research purposes
Measurable disease as defined by a lymph node or tumor mass that is >= 1.5 cm in at least one dimension by CT or the CT portion of the PET/CT
Absolute neutrophil count >= 750/mm^3 (0.75 x 10^9/L)
...
Willingness to provide biologic samples for correlative research purposes
Measurable disease as defined by a lymph node or tumor mass that is >= 1.5 cm in at least one dimension by CT or the CT portion of the PET/CT
Absolute neutrophil count >= 750/mm^3 (0.75 x 10^9/L)
Negative serum pregnancy test done =< 7 days prior to registration for women of childbearing potential only
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) unless Gilbert's syndrome or disease infiltration of the liver is present
Relapsed or refractory follicular lymphoma which has progressed during or following 1 or more prior chemotherapy regimens for lymphoma
Note: Fresh (frozen) tumor biopsy must be available or attempted; a frozen tumor biopsy equivalent to a minimum of four at least 16 gauge needle cores is an important component of this study; patients without adequate frozen material should have a biopsy performed to obtain material; if biopsy is performed and does not yield adequate material, the patient is still eligible for the study; if a biopsy cannot be done safely, the patient may still be eligible for the study if permission is granted in writing (email) by the study chair (Dr. Nancy Bartlett) or her designees; Dr. Bartlett may be consulted to discuss situations involving invasive biopsy procedures that may pose an increased risk to the patient
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
Platelets >= 30,000/mm^3 (30 x 10^9/L)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 x institutional ULN
Creatinine =< 2.0 x institutional ULN
Creatinine clearance (estimated [est.] glomerular filtration rate [GFR] Cockcroft-Gault) >= 30 mL/min
Ability to understand and the willingness to sign a written informed consent document
Hemoglobin >= 8.0 g/dL

Exclusion Criteria

Note: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ibrutinib administration
Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450 family 3 subfamily A member 4/5 (CYP3A4/5)
...
Note: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of ibrutinib administration
Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450 family 3 subfamily A member 4/5 (CYP3A4/5)
Concurrent treatment with therapeutic doses (> 20 mg prednisone or equivalent) of systemic steroids within 14 days of start of protocol therapy
Nursing women
Receiving any other investigational agents
Prior history of allogeneic stem cell transplant
Note: HIV-positive patients who are not on anti-viral medications that are strong CYP3A4/5 inhibitors and who do not have cluster of differentiation (CD)4 counts less than the lower limit of normal by institutional criteria are eligible; no patients with CD4 counts below institutional normals are eligible
Note: Breastfeeding should be discontinued if the mother is treated with ibrutinib
Cardiac disease
Psychiatric illness/social situations that would limit compliance with study requirements
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib
Pregnant women
Uncontrolled diabetes mellitus
Active central nervous system (CNS) involvement
Radiotherapy =< 4 weeks prior to registration
Known active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
Major surgery =< 10 days prior to registration or minor surgery =< 7 days prior to registration
Note: Patients are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy, and are considered by their physician to be at less than 30% risk of relapse
Ongoing or active infection,
Prior therapy with ibrutinib or another Bruton's tyrosine kinase inhibitor
Chemotherapy/systemic therapy =< 4 weeks prior to registration
History of stroke or intracranial hemorrhage =< 6 months prior to the first dose of study drug
Patient has the inability to swallow tablets
Nitrosoureas or mitomycin C =< 6 weeks prior to registration
Note: Warfarin or similar vitamin K antagonist must have been discontinued at least 28 days prior to study entry
Note: A prior history of adequately treated transformed lymphoma does not exclude a patient if the current active disease is biopsy-proven follicular lymphoma

Locations

Singapore, 119074
Philadelphia, Pennsylvania, 19111
Saint Louis Park, Minnesota, 55416
Singapore, 169610
Kingston, Ontario, K7L 2V7
...
Singapore, 119074
Philadelphia, Pennsylvania, 19111
Saint Louis Park, Minnesota, 55416
Singapore, 169610
Kingston, Ontario, K7L 2V7
Madison, Wisconsin, 53792
Jacksonville, Florida, 32224-9980
Saint Louis, Missouri, 63110
Saint Louis Park, Minnesota, 55416
Hamilton, Ontario, L8V 5C2
Rochester, Minnesota, 55905
Toronto, Ontario, M5G 2M9
Scottsdale, Arizona, 85259

Tracking Information

NCT #
NCT01849263
Collaborators
Not Provided
Investigators
  • Principal Investigator: Nancy L Bartlett Mayo Clinic
  • Nancy L Bartlett Mayo Clinic