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Ibrutinib and Palbociclib Isethionate in Treating Patients With Previously Treated Mantle Cell Lymphoma
Conditions
Recurrent Mantle Cell Lymphoma
Conditions: official terms
Lymphoma - Lymphoma, Mantle-Cell
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Ibrutinib
Type: Drug
Name: Laboratory Biomarker Analysis
Type: Other
Name: Palbociclib
Type: Drug
Name: Pharmacological Study
Type: Other
Overall Status
Recruiting
Summary
This phase I trial studies the side effects and best dose of ibrutinib and palbociclib isethionate in treating patients with previously treated mantle cell lymphoma. Ibrutinib and palbociclib isethionate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Palbociclib isethionate may also help ibrutinib work better by making cancer cells more sensitive to the drug.
Detailed Description
PRIMARY OBJECTIVES:
I. To evaluate the safety of ibrutinib plus PD 0332991 (palbociclib [palbociclib isethionate]) in patients with previously treated mantle cell lymphoma (MCL) and select the recommended phase 2 dose schedule.
SECONDARY OBJECTIVES:
I. To estimate the toxicity profile of ibrutinib plus PD 0332991 (palbociclib). II. To estimate the overall response rate (ORR) and complete response (CR) rates.
III. To estimate the progression-free survival (PFS). IV. To estimate the response duration (RD).
TERTIARY OBJECTIVES:
I. To evaluate the genomic profile of MCL cells pre-treatment and at relapse. II. To estimate the pharmacokinetic profile of concurrent ibrutinib and PD 0332991 (palbociclib).
OUTLINE: This is a dose-escalation study.
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 and palbociclib isethionate PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 2 years.
I. To evaluate the safety of ibrutinib plus PD 0332991 (palbociclib [palbociclib isethionate]) in patients with previously treated mantle cell lymphoma (MCL) and select the recommended phase 2 dose schedule.
SECONDARY OBJECTIVES:
I. To estimate the toxicity profile of ibrutinib plus PD 0332991 (palbociclib). II. To estimate the overall response rate (ORR) and complete response (CR) rates.
III. To estimate the progression-free survival (PFS). IV. To estimate the response duration (RD).
TERTIARY OBJECTIVES:
I. To evaluate the genomic profile of MCL cells pre-treatment and at relapse. II. To estimate the pharmacokinetic profile of concurrent ibrutinib and PD 0332991 (palbociclib).
OUTLINE: This is a dose-escalation study.
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 and palbociclib isethionate PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 2 years.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:
- Patients must have histologically or cytologically confirmed mantle cell lymphoma as defined by the World Health Organization; all patients must have either t(11;14) by karyotype or fluorescent in-situ hybridization (FISH) or positive immunohistochemistry for cyclin D1
- Subjects must have measureable disease defined as at least one tumor lesion of at least 1.5 cm or a peripheral blood cluster of differentiation (CD)5+, CD19+ lymphocyte count of at least 5,000 cells/uL
- Subjects must have received at least one prior treatment regimen
- Subjects that have received prior ibrutinib or PD 0332991 (palbociclib) are ineligible
- Subjects that have undergone prior allogeneic stem cell transplantation will only be eligible if the transplant occurred at least 1 year prior to study entry, the patient is no longer taking any immunosuppressive therapy, and there are no significant ongoing transplant-related adverse effects
- Subjects who have had chemotherapy, radiotherapy, antibodies, or investigational agents within 4 weeks prior to entering the study unless progression has been documented while on treatment and all treatment-related toxicities have resolved to pre-treatment baseline; subjects may be receiving equivalent to prednisone at a maximum dose of 20 mg/day orally
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Absolute neutrophil count (ANC) >= 750 cells/uL
- Platelets >= 50,000 cells/uL
- Total bilirubin =< 1.5 times upper limit of normal unless due to Gilbert's disease
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times upper limit of normal
- Calculated creatinine clearance >= 60 mL/min by Cockcroft-Gault
- Corrected QT interval (QTc) =< 480 ms
- Subjects with known or suspected central nervous system (CNS) involvement are not eligible
- Subjects with serologic status reflecting active viral hepatitis B or C infection are not eligible; subjects that are hepatitis B core antibody positive but antigen negative will need negative polymerase chain reaction (PCR) prior to enrollment; hepatitis B antigen or PCR-positive patients will be excluded
- Subjects with uncontrolled human immunodeficiency virus (HIV) are not eligible; controlled HIV is defined as a CD4 count > institutional lower limit of normal and no current co-infection; uncontrolled HIV is all other HIV infection; note that patients with controlled infection should be allowed to participate only if they are not receiving prohibited cytochrome P450 (CYP) interactive medications
- Subjects unable to swallow capsules or with disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption, such as malabsorption syndrome, resection of small bowel, or poorly controlled inflammatory bowel disease affecting the small intestine are not eligible
- Subjects with uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible
- Subjects with uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in declining platelet or hemoglobin levels within the 4 weeks prior to first dose of study drug are not eligible
- Patients with transfusion-dependent thrombocytopenia are not eligible
- Subjects with myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities are not eligible; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
- Subjects with a history of stroke or intracranial hemorrhage within 6 months prior to enrollment are not eligible
- Subjects with a history of malignancy are not eligible with the exception of the following:
- Malignancy treated within curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
- Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
- Adequately treated cervical carcinoma in situ without current evidence of disease
- 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; subjects should be offered the opportunity to bank sperm or eggs prior to initiation of study drug
- Female subjects that are pregnant or breastfeeding are not eligible
- Subjects that have received anticoagulation therapy with warfarin or equivalent vitamin K antagonists within the last 28 days are not eligible
- Subjects with a bleeding diathesis are not eligible
- Subjects receiving other investigational agents are not eligible
- Subjects should be willing to undergo a research related biopsy prior to treatment and at the time of progression
- Subjects must give informed consent and must be willing and able to comply with the scheduled visits, treatment plans, laboratory tests, and other procedures
- Patients must have histologically or cytologically confirmed mantle cell lymphoma as defined by the World Health Organization; all patients must have either t(11;14) by karyotype or fluorescent in-situ hybridization (FISH) or positive immunohistochemistry for cyclin D1
- Subjects must have measureable disease defined as at least one tumor lesion of at least 1.5 cm or a peripheral blood cluster of differentiation (CD)5+, CD19+ lymphocyte count of at least 5,000 cells/uL
- Subjects must have received at least one prior treatment regimen
- Subjects that have received prior ibrutinib or PD 0332991 (palbociclib) are ineligible
- Subjects that have undergone prior allogeneic stem cell transplantation will only be eligible if the transplant occurred at least 1 year prior to study entry, the patient is no longer taking any immunosuppressive therapy, and there are no significant ongoing transplant-related adverse effects
- Subjects who have had chemotherapy, radiotherapy, antibodies, or investigational agents within 4 weeks prior to entering the study unless progression has been documented while on treatment and all treatment-related toxicities have resolved to pre-treatment baseline; subjects may be receiving equivalent to prednisone at a maximum dose of 20 mg/day orally
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Absolute neutrophil count (ANC) >= 750 cells/uL
- Platelets >= 50,000 cells/uL
- Total bilirubin =< 1.5 times upper limit of normal unless due to Gilbert's disease
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times upper limit of normal
- Calculated creatinine clearance >= 60 mL/min by Cockcroft-Gault
- Corrected QT interval (QTc) =< 480 ms
- Subjects with known or suspected central nervous system (CNS) involvement are not eligible
- Subjects with serologic status reflecting active viral hepatitis B or C infection are not eligible; subjects that are hepatitis B core antibody positive but antigen negative will need negative polymerase chain reaction (PCR) prior to enrollment; hepatitis B antigen or PCR-positive patients will be excluded
- Subjects with uncontrolled human immunodeficiency virus (HIV) are not eligible; controlled HIV is defined as a CD4 count > institutional lower limit of normal and no current co-infection; uncontrolled HIV is all other HIV infection; note that patients with controlled infection should be allowed to participate only if they are not receiving prohibited cytochrome P450 (CYP) interactive medications
- Subjects unable to swallow capsules or with disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption, such as malabsorption syndrome, resection of small bowel, or poorly controlled inflammatory bowel disease affecting the small intestine are not eligible
- Subjects with uncontrolled illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible
- Subjects with uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP) resulting in declining platelet or hemoglobin levels within the 4 weeks prior to first dose of study drug are not eligible
- Patients with transfusion-dependent thrombocytopenia are not eligible
- Subjects with myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities are not eligible; prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
- Subjects with a history of stroke or intracranial hemorrhage within 6 months prior to enrollment are not eligible
- Subjects with a history of malignancy are not eligible with the exception of the following:
- Malignancy treated within curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
- Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
- Adequately treated cervical carcinoma in situ without current evidence of disease
- 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; subjects should be offered the opportunity to bank sperm or eggs prior to initiation of study drug
- Female subjects that are pregnant or breastfeeding are not eligible
- Subjects that have received anticoagulation therapy with warfarin or equivalent vitamin K antagonists within the last 28 days are not eligible
- Subjects with a bleeding diathesis are not eligible
- Subjects receiving other investigational agents are not eligible
- Subjects should be willing to undergo a research related biopsy prior to treatment and at the time of progression
- Subjects must give informed consent and must be willing and able to comply with the scheduled visits, treatment plans, laboratory tests, and other procedures
Locations
Cleveland Clinic
Fort Lauderdale, Florida, United States
University of Chicago Comprehensive Cancer Center
Status: Not yet recruiting
Contact: Peter Martin - 646-962-2064 - pem9019@med.cornell.edu
Chicago, Illinois, United States
Dana-Farber Harvard Cancer Center
Status: Recruiting
Contact: Sonali M. Smith - 773-834-2895 - smsmith@medicine.bsd.uchicago.edu
Boston, Massachusetts, United States
Washington University School of Medicine
Status: Recruiting
Contact: Ann S. LaCasce - 617-632-5959 - Ann_LaCasce@dfci.harvard.edu
Saint Louis, Missouri, United States
Weill Medical College of Cornell University
Status: Recruiting
Contact: Nancy L. Bartlett - 314-362-5654 - nbartlet@DOM.wustl.edu
New York, New York, United States
University of North Carolina at Chapel Hill
Status: Recruiting
Contact: Peter Martin - 646-962-2064 - pem9019@med.cornell.edu
Chapel Hill, North Carolina, United States
Duke University Medical Center
Status: Recruiting
Contact: Steven I. Park - 919-843-5968 - sipark@med.unc.edu
Durham, North Carolina, United States
Ohio State University Comprehensive Cancer Center
Status: Recruiting
Contact: Anne W. Beaven - 919-684-8964 - anne.beaven@duke.edu
Columbus, Ohio, United States
Status: Recruiting
Contact: John C. Byrd - 614-293-9869 - john.byrd@osumc.edu
Start Date
May 2014
Sponsors
National Cancer Institute (NCI)
Source
National Cancer Institute (NCI)
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page