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Recurrent Mantle Cell LymphomaPhase 1NCT02159755

Ibrutinib and Palbociclib in Treating Patients With Previously Treated Mantle Cell Lymphoma

A Phase 1 study testing Ibrutinib, Laboratory Biomarker Analysis and Palbociclib in people with Recurrent Mantle Cell Lymphoma, run by National Cancer Institute (NCI) at 4 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Recurrent Mantle Cell Lymphoma
What is being tested?
Ibrutinib, Laboratory Biomarker Analysis and Palbociclib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
4 sitesUnited States
Study dates
13 Aug 2014to 30 Apr 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase I Trial of Ibrutinib Plus PD 0332991 (Palbociclib) in Patients With Previously Treated Mantle Cell Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Ibrutinib, Laboratory Biomarker Analysis, Palbociclib, Pharmacological Study
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PalbociclibDrug

    Also called 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991

    Given PO

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT02159755
Study groupRoleWhat they receive
Treatment (ibrutinib, palbociclib)ExperimentalPatients receive ibrutinib PO 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.
Receives: Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Drug: Palbociclib; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended phase II dose of the combination of ibrutinib and palbociclib

    Will be defined as the highest dose level at which no more than 1/6 patients present with a dose limiting toxicity (DLT). DLT will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: Up to 28 days

Secondary outcomes (6)

  1. Overall response rate (ORR)

    Will be evaluated according to the revised response criteria of the International Working Group.

    Measured: Up to 2 years

  2. Complete response (CR) rate

    Will be evaluated according to the revised response criteria of the International Working Group.

    Measured: Up to 2 years

  3. Partial response rate

    Will be evaluated according to the revised response criteria of the International Working Group.

    Measured: Up to 2 years

  4. Progression-free survival (PFS)

    Estimated and plotted by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. Log-rank test will be applied to compare the difference between survival curves with two-sided significance level of 0.05.

    Measured: Time from entry onto study until first documentation of objective tumor progression or death due to any cause, whichever occurs first, assessed up to 2 years

  5. Response duration (RD)

    Estimated and plotted by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. Log-rank test will be applied to compare the difference between survival curves with two-sided significance level of 0.05.

    Measured: Time from when criteria for response (CR or partial response [PR]) are met, until first documentation of relapse or progression, assessed up to 2 years

  6. Incidence of toxicities

    Will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. A listing of all adverse events (AEs) including detailed information for each AE will be presented. The number and percentage of patients who experienced any: AE, serious adverse events (SAE), treatment-related AE, and treatment-related SAE will be summarized. AE data will be presented by dose for all cycles, cycle 1 only and cycles > 1, as appropriate. Additional summaries of AE data and of other safety data will be presented in tabular and/or graphical format and summarized descriptively, as appropriate.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jun 2014 (estimated)
  2. Study start13 Aug 2014
  3. Primary completion25 Jun 2018
  4. Study completion30 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02159755
Sponsor's protocol ID
NCI-2014-01202
Other IDs
NCI-2014-01202, 1403014853, 9534, 9534, K24CA201524, UM1CA186704, UM1CA186712
Status last verified
May 2026
First submitted
9 Jun 2014
Last updated
27 May 2026
Results posted
No
Data monitoring committee
No

Publications

  • Martin P, Bartlett NL, Blum KA, Park S, Maddocks K, Ruan J, Ridling L, Dittus C, Chen Z, Huang X, Inghirami G, DiLiberto M, Chen-Kiang S, Leonard JP. A phase 1 trial of ibrutinib plus palbociclib in previously treated mantle cell lymphoma. Blood. 2019 Mar 14;133(11):1201-1204. doi: 10.1182/blood-2018-11-886457. Epub 2019 Jan 28.

    PubMed 30692121

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ibrutinib, Laboratory Biomarker Analysis and Palbociclib in people with Recurrent Mantle Cell Lymphoma, run by National Cancer Institute (NCI) at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended phase II dose of the combination of ibrutinib and palbociclib (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02159755, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2026.

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