Trial Title:
Ibrutinib and Palbociclib in Treating Patients With Previously Treated Mantle Cell Lymphoma
NCT ID:
NCT02159755
Condition:
Recurrent Mantle Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Mantle-Cell
Palbociclib
Ibrutinib
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ibrutinib
Description:
Given PO
Arm group label:
Treatment (ibrutinib, palbociclib)
Other name:
BTK Inhibitor PCI-32765
Other name:
CRA 032765
Other name:
CRA-032765
Other name:
CRA032765
Other name:
Imbruvica
Other name:
PCI 32765
Other name:
PCI-32765
Other name:
PCI32765
Intervention type:
Other
Intervention name:
Laboratory Biomarker Analysis
Description:
Correlative studies
Arm group label:
Treatment (ibrutinib, palbociclib)
Intervention type:
Drug
Intervention name:
Palbociclib
Description:
Given PO
Arm group label:
Treatment (ibrutinib, palbociclib)
Other name:
6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one
Other name:
Ibrance
Other name:
PD 0332991
Other name:
PD 332991
Other name:
PD 991
Other name:
PD-0332991
Other name:
PD0332991
Intervention type:
Other
Intervention name:
Pharmacological Study
Description:
Correlative studies
Arm group label:
Treatment (ibrutinib, palbociclib)
Summary:
This phase I trial studies the side effects and best dose of ibrutinib and palbociclib in
treating patients with previously treated mantle cell lymphoma. Ibrutinib and palbociclib
may stop the growth of cancer cells by blocking some of the enzymes needed for cell
growth. Palbociclib may also help ibrutinib work better by making cancer cells more
sensitive to the drug.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the safety of ibrutinib plus PD 0332991 (palbociclib) 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).
LABORATORY OBJECTIVES:
I. To evaluate the genomic profile of MCL cells pre-treatment and at relapse. II. To
estimate the pharmacokinetic profile of ibrutinib when given concurrently with PD 0332991
(palbociclib).
III. To evaluate the level of cell-free tumor deoxyribonucleic acid (DNA) over time in
conjunction with response to therapy.
IV. To evaluate the presence of circulating MCL cells over time.
OUTLINE: This is a dose-escalation study.
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 and palbociclib PO QD
on days 1-21. Cycles 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:
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 measurable disease defined as at least one tumor lesion of at
least 1.5 cm or a peripheral blood CD5+, CD19+ lymphocyte count of at least 5,000
cells/uL
- Subjects must have received at least one prior treatment regimen
- Subjects that have received a prior BTK inhibitor or CDK4/6 inhibition 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 must not have received chemotherapy =< 21 days prior to first
administration of study treatment, monoclonal antibody =< 6 weeks prior to
first administration of study treatment, and/or radiotherapy or other
investigational agents =< 4 weeks prior to first administration study treatment
unless the subjects' tumor has progressed on the previous therapy and the
investigator believes that the patient should not postpone further therapy and,
all treatment-related toxicities have resolved to Common Terminology Criteria
for Adverse Events (CTCAE) version (v) 5 =< grade 1; subjects may be receiving
equivalent to prednisone at a maximum dose of 20 mg/day orally
- Subjects must be age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Patients must have normal organ and marrow function, independent of transfusion or
growth factor support within 14 days before enrollment; patients should not receive
growth factors or transfusions for at least 7 days prior to the first dose of study
drug, with the exception of pegylated GCSF (pegfilgrastim) and darbepoetin, which
require at least 14 days prior to screening and enrollment
- Absolute neutrophil count (ANC) >= 750 cells/uL (within 14 days before enrollment)
- Platelets >= 50,000 cells/uL (within 14 days before enrollment)
- Total bilirubin =< 1.5 times upper limit of normal unless due to Gilbert's disease
(within 14 days before enrollment)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase
[SGPT]) =< 2.5 times upper limit of normal (within 14 days before enrollment)
- Calculated creatinine clearance >= 30 mL/min by Cockcroft-Gault (within 14 days
before enrollment)
- Corrected QT interval (QTc) =< 480 ms (within 14 days before enrollment)
- Prothrombin time (PT)/international normalized ratio (INR) < 1.5 times upper limit
of normal (within 14 days before enrollment)
- Partial thromboplastin time (PTT) < 1.5 times upper limit of normal (within 14 days
before enrollment)
- The effects of ibrutinib and PD 0332991 (palbociclib) on the developing human fetus
are unknown; for this reason and because tyrosine kinase inhibitors as well as other
therapeutic agents used in this trial may be teratogenic, 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; female patients who are of non-reproductive potential include
the following: post-menopausal by history - no menses for >= 1 year; OR history of
hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral
oophorectomy); female patients of childbearing potential must have a negative serum
pregnancy test upon study entry; male and female patients who agree to use highly
effective methods of birth control (e.g., condoms, implants, injectables, combined
oral contraceptives, some intrauterine devices [IUDs], complete sexual abstinence,
or sterilized partner) during the period of therapy and for 90 days after the last
dose of study drug
- 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
- Subjects with currently active, clinically significant hepatic impairment (>
moderate hepatic impairment according to the National Cancer Institute (NCI)/Child
Pugh classification)
- Subjects requiring daily corticosteroids at a prednisone equivalent of > 20 mg daily
should not be enrolled; if corticosteroids can be discontinued (or reduced to < 20
mg per day or prednisone equivalent), the discontinuation or dose reduction should
be done at least 7 days prior to the first dose
- 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
Exclusion Criteria:
- 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 positive for hepatitis B core antibody positive
hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative
polymerase chain reaction (PCR) prior to enrollment. (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 the stomach or small bowel, partial or complete
bowel obstruction, or symptomatic inflammatory bowel disease 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; recent infections requiring systemic
treatment need to have completed therapy > 14 days before the first dose of the
study drugs
- 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 acute coronary syndrome 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
- 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 (e.g., von Willebrand's disease or hemophilia)
are not eligible
- Subjects that have undergone major surgery within 4 weeks prior to the first dose of
study drug are not eligible
- Subjects receiving other investigational agents are not eligible
- Subjects who received a strong CYP3A inhibitor within 7 days prior to the first dose
of study drug, or patients who require continuous treatment with a strong CYP3A
inhibitor are not eligible
- Subjects receiving systemic immunosuppressant therapy (e.g., cyclosporine,
tacrolimus, etc.) within 28 days of the first dose of study drug are not eligible
- Subjects that have been vaccinated with live, attenuated vaccines within 4 weeks of
the first dose of study drug are not eligible
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Facility:
Name:
NYP/Weill Cornell Medical Center
Address:
City:
New York
Zip:
10065
Country:
United States
Facility:
Name:
UNC Lineberger Comprehensive Cancer Center
Address:
City:
Chapel Hill
Zip:
27599
Country:
United States
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Start date:
May 20, 2014
Completion date:
January 20, 2025
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT02159755
