Recruitment

Recruitment Status
Active, not recruiting

Inclusion Criteria

Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.5 x ULN
Understand and voluntarily sign an informed consent form
Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL), confirmed by flow cytometry and as per the criteria outlined by the IWCLL/Hallek December 2008
...
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.5 x ULN
Understand and voluntarily sign an informed consent form
Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL), confirmed by flow cytometry and as per the criteria outlined by the IWCLL/Hallek December 2008
Prior frontline therapy for B-CLL must have been discontinued >= 56 days but =< 365 days prior to registration; NOTE: Patients on supportive care therapy due to use of specific induction regimen such as antibiotics may continue on those treatments at the discretion of the treating physician
Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
Able to adhere to the study visit schedule and other protocol requirements including willing to provide blood, baseline bone marrow aspirate, and control deoxyribonucleic acid (DNA) samples for correlative research purposes
Platelet count >= 30,000/mm^3
Total bilirubin =< 1.5 mg/dL or direct bilirubin =< 1.0 mg/dL for patients with Gilbert's syndrome
Patients must have a sustained clinical response (PR, nodular PR [nPR], complete clinical response [CCR], CR with incomplete marrow recovery [CRi], CR) with documented residual disease (>= 1 CLL cell per 10,000 leukocytes or >= 0.01% MRD) either in the blood, bone marrow or a lymph node >= 3.5 cm by any available techniques
Serum creatinine =< 1.5 x upper limit of normal (ULN)
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 at registration
Patient must have completed a frontline induction therapy (minimum of 2 treatment cycles); NOTE: Standard therapies/therapeutic agents are defined as those listed in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of CLL; also, patients who received induction regimen as part of a clinical trial and is not necessarily mentioned in the NCCN guidelines, will also be eligible as long as the patient has completed at least 2 treatment cycles of induction regimen, achieved a clinical response (PR or CR) and is able to meet all other criteria for the study; however, patients who have previously received ibrutinib or have been randomized to ibrutinib containing arms in a clinical trial will not be eligible for this study
Absolute neutrophil count >= 1000/mm^3

Exclusion Criteria

Patients with history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix, unless in complete remission and off therapy for that disease for > 3 years)
Pregnant women
Nursing women
...
Patients with history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix, unless in complete remission and off therapy for that disease for > 3 years)
Pregnant women
Nursing women
Major surgery =< 4 weeks prior to registration
Patients who have received more than 1 prior therapy; NOTE: Prior therapy is defined as any single agent or combination regimen that is included as treatment for symptomatic CLL; treatment(s) given prior to the symptomatic phase of the disease (preventive strategy) will not be considered as prior induction therapy; for the purpose of a particular therapy/regimen to be counted towards the number of prior treatments a patient must have received at least 2 cycles of the induction regimen e.g., a patient who change their treatment regimen after only 1 cycle (due to toxicity or any other reason) will not be considered to have "2" prior therapies
Patients who have progressive disease or relapse (as defined by the IWCLL criteria) at or any time before registration on this study
Patients who are already MRD- (both in the blood and the bone marrow) after frontline therapy and have lymph nodes < 3.5 cm
Men or women of childbearing potential who are unwilling to employ adequate contraception
Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification
Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
Patients with other diseases that in the opinion of the treating physician pose a higher risk for treatment with ibrutinib therapy including active human immunodeficiency virus (HIV) infection and bleeding disorders
Requires treatment with a strong cytochrome P450 modulators (cytochrome P450, family 3, subfamily A [CYP3A] inhibitor and/or CYP3A inducers)
Use of any other experimental drug or therapy =< 28 days prior to registration on this study; NOTE: Patients on low dose prednisone (=< 10 mg) for treatment of conditions other than CLL are eligible
Patients who have active infectious hepatitis
Concomitant use of warfarin or other vitamin K antagonists
Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

Summary

Conditions
  • Stage I Chronic Lymphocytic Leukemia
  • Stage II Chronic Lymphocytic Leukemia
  • Stage III Chronic Lymphocytic Leukemia
  • Stage IV Chronic Lymphocytic Leukemia
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. Determine the rate of minimal residual disease (MRD)-negative responses (in both blood and bone marrow) at any time during treatment with ibrutinib maintenance. SECONDARY OBJECTIVES: I. Median time to achieve MRD- (negative) status (in blood and in bone marrow) after initiatio...

PRIMARY OBJECTIVES: I. Determine the rate of minimal residual disease (MRD)-negative responses (in both blood and bone marrow) at any time during treatment with ibrutinib maintenance. SECONDARY OBJECTIVES: I. Median time to achieve MRD- (negative) status (in blood and in bone marrow) after initiation of ibrutinib maintenance treatment. II. Toxicity profile of ibrutinib as maintenance therapy after frontline induction. III. Durability of the MRD- state (determined from the time of first documentation of MRD- until the first documentation of MRD+ (positive) (or last date shown to be MRD- for a censor). IV. Determine the number of patients who improve their remission category (i.e., upgrade clinical response achieved after the induction such as from partial response [PR] to complete response [CR]) after initiating the maintenance therapy. V. Time to requirement of next therapy for patients who achieve confirmed MRD- vs. those who remain MRD+ disease at 48 weeks (end of 12 cycles). VI. Progression free survival (as determined by the International Workshop on Chronic Lymphocytic Leukemia [IWCLL] criteria) among patients who achieve confirmed MRD- vs. those who remain MRD+ disease at 48 weeks (end of 12 cycles). TERTIARY OBJECTIVES: I. To conduct correlative studies for further understanding of the mechanism of antitumor activity of ibrutinib in eradication of the MRD. II. Determine the impact of ibrutinib on depression and anxiety symptoms to better understand toxicity profile of ibrutinib maintenance. III. Determine impact of social support or lack thereof on mood symptoms in chronic lymphocytic leukemia (CLL) patients receiving maintenance treatment. OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Treatment repeats every 4 weeks* for up to 36 courses in the absence of disease progression or unacceptable toxicity. Note: *The last course may last up to 56 days to accommodate the study drug discontinuation visit. After completion of study treatment, patients are followed up every 3-6 months for up to 2 years.

Inclusion Criteria

Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.5 x ULN
Understand and voluntarily sign an informed consent form
Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL), confirmed by flow cytometry and as per the criteria outlined by the IWCLL/Hallek December 2008
...
Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.5 x ULN
Understand and voluntarily sign an informed consent form
Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL), confirmed by flow cytometry and as per the criteria outlined by the IWCLL/Hallek December 2008
Prior frontline therapy for B-CLL must have been discontinued >= 56 days but =< 365 days prior to registration; NOTE: Patients on supportive care therapy due to use of specific induction regimen such as antibiotics may continue on those treatments at the discretion of the treating physician
Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
Able to adhere to the study visit schedule and other protocol requirements including willing to provide blood, baseline bone marrow aspirate, and control deoxyribonucleic acid (DNA) samples for correlative research purposes
Platelet count >= 30,000/mm^3
Total bilirubin =< 1.5 mg/dL or direct bilirubin =< 1.0 mg/dL for patients with Gilbert's syndrome
Patients must have a sustained clinical response (PR, nodular PR [nPR], complete clinical response [CCR], CR with incomplete marrow recovery [CRi], CR) with documented residual disease (>= 1 CLL cell per 10,000 leukocytes or >= 0.01% MRD) either in the blood, bone marrow or a lymph node >= 3.5 cm by any available techniques
Serum creatinine =< 1.5 x upper limit of normal (ULN)
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 at registration
Patient must have completed a frontline induction therapy (minimum of 2 treatment cycles); NOTE: Standard therapies/therapeutic agents are defined as those listed in the National Comprehensive Cancer Network (NCCN) guidelines for treatment of CLL; also, patients who received induction regimen as part of a clinical trial and is not necessarily mentioned in the NCCN guidelines, will also be eligible as long as the patient has completed at least 2 treatment cycles of induction regimen, achieved a clinical response (PR or CR) and is able to meet all other criteria for the study; however, patients who have previously received ibrutinib or have been randomized to ibrutinib containing arms in a clinical trial will not be eligible for this study
Absolute neutrophil count >= 1000/mm^3

Exclusion Criteria

Patients with history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix, unless in complete remission and off therapy for that disease for > 3 years)
Pregnant women
Nursing women
...
Patients with history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix, unless in complete remission and off therapy for that disease for > 3 years)
Pregnant women
Nursing women
Major surgery =< 4 weeks prior to registration
Patients who have received more than 1 prior therapy; NOTE: Prior therapy is defined as any single agent or combination regimen that is included as treatment for symptomatic CLL; treatment(s) given prior to the symptomatic phase of the disease (preventive strategy) will not be considered as prior induction therapy; for the purpose of a particular therapy/regimen to be counted towards the number of prior treatments a patient must have received at least 2 cycles of the induction regimen e.g., a patient who change their treatment regimen after only 1 cycle (due to toxicity or any other reason) will not be considered to have "2" prior therapies
Patients who have progressive disease or relapse (as defined by the IWCLL criteria) at or any time before registration on this study
Patients who are already MRD- (both in the blood and the bone marrow) after frontline therapy and have lymph nodes < 3.5 cm
Men or women of childbearing potential who are unwilling to employ adequate contraception
Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification
Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
Patients with other diseases that in the opinion of the treating physician pose a higher risk for treatment with ibrutinib therapy including active human immunodeficiency virus (HIV) infection and bleeding disorders
Requires treatment with a strong cytochrome P450 modulators (cytochrome P450, family 3, subfamily A [CYP3A] inhibitor and/or CYP3A inducers)
Use of any other experimental drug or therapy =< 28 days prior to registration on this study; NOTE: Patients on low dose prednisone (=< 10 mg) for treatment of conditions other than CLL are eligible
Patients who have active infectious hepatitis
Concomitant use of warfarin or other vitamin K antagonists
Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

Locations

Jacksonville, Florida, 32224-9980
Jacksonville, Florida, 32224-9980

Tracking Information

NCT #
NCT02649387
Collaborators
National Cancer Institute (NCI)
Investigators
  • Principal Investigator: Asher Chanan-Khan Mayo Clinic
  • Asher Chanan-Khan Mayo Clinic