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Ibrutinib in Treating Participants With Untreated High Risk Smoldering Mantle Cell Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03282396
Recruitment Status : Recruiting
First Posted : September 13, 2017
Last Update Posted : June 18, 2020
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies how well ibrutinib works in treating participants with untreated high risk smoldering mental cell lymphoma. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or disease Intervention/treatment Phase
Mantle Cell Lymphoma Drug: Ibrutinib Phase 2

Detailed Description:


I. To measure the progression-free survival (PFS) in previously untreated high-risk smoldering mental cell lymphoma (MCL) patients treated with ibrutinib.


I. To evaluate the safety of ibrutinib in previously untreated high risk smoldering MCL.

II. To evaluate the response rate and duration of response of ibrutinib. III. To study clonal evolution in MCL while under ibrutinib.


I. To collect serial samples for our correlative study (plasma, peripheral blood mononuclear cells [PBMC], initial tumor biopsy).


Participants receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days for 5 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up every 2 months for 6 months, every 2-4 months for 2 years, then every 4-6 months thereafter.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Ibrutinib in Perviously Untreated High Risk Smoldering Mantle Cell Lymphoma (MCL)
Actual Study Start Date : June 8, 2020
Estimated Primary Completion Date : February 28, 2022
Estimated Study Completion Date : February 28, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Ibrutinib

Arm Intervention/treatment
Experimental: Treatment (ibrutinib)
Participants receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days for 5 years in the absence of disease progression or unacceptable toxicity.
Drug: Ibrutinib
Given PO
Other Names:
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • Imbruvica
  • PCI-32765

Primary Outcome Measures :
  1. Progression free survival [ Time Frame: Up to 3.5 years ]
    Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.

Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 3.5 years ]
    Logistic regression will be utilized to assess the effect of patient prognostic factors on the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.

  2. Response rate of ibrutinib [ Time Frame: Up to 3.5 years ]
    Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate.

  3. Response duration [ Time Frame: Up to 3.5 years ]
    Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.

  4. Overall survival [ Time Frame: Up to 3.5 years ]
    Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Confirmed diagnosis of MCL with CD20 and cyclin D1 positivity in tissue biopsy. Patients must have never received any prior therapy for their disease. Patients have been observed for 3 - 6 months with no progression as per imaging assessments
  • High risk smoldering MCL: non-blastoid variant histology, non-pleomorphic variant histology with a Ki-67 of 20-30% and absence of B symptoms with/without white blood cell (WBC) 15-30k, lymph nodes =< 5 cm in diameter, non-blastoid/pleomorphic with a complex karyotype, TP53 mutated or wild type, del17p (fluorescence in situ hybridization [FISH]% 10-50%), MYC positive , presence of NOTCH2, NSD2 or more than one mutation in the initial next generation sequencing (NGS) panel testing but who are asymptomatic and do not have any clinical indication to start systemic therapy
  • Understand and voluntarily sign an institutional review board (IRB)-approved informed consent form
  • Patients should in general have bi-dimensional measurable disease with their biggest tumor less than or equal to 5 cm. (Bone marrow or gastrointestinal [GI] only involvement is acceptable)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
  • With minimal disease related symptoms but anxious to start systemic therapy
  • Absence of cytopenia attributed to bone marrow (BM) infiltration
  • Absolute neutrophil count (ANC) > 1000/mm^3
  • Platelet count > 100,000/mm^3
  • Patients who have bone marrow infiltration by MCL are eligible if their ANC is >= than 500 or their platelet level is >= than 50,000 /mm^3. Platelet transfusions are allowed
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) < 3 x upper limit of normal or < 5 x upper limit of normal if hepatic metastases are present
  • Serum bilirubin < 1.5 mg/dl
  • Creatinine (Cr) clearance >= 30 mL/min
  • Disease free of prior malignancies of equal to or greater than 6 months with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated. Patients must be willing to receive transfusions of blood products
  • Willing and able to participate in all study related procedures and therapy including swallowing capsules without difficulty and having a screening core biopsy
  • Female subjects who are of non-reproductive potential (i.e., 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 subjects of childbearing potential must have a negative serum pregnancy test upon study entry
  • Male and female subjects who agree to use highly effective methods of birth control (e.g., implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner) and a barrier method (e.g., condoms, vaginal ring, sponge, etc) during the period of therapy and for 30 days after the last dose of study drug for females and 90 days for males

Exclusion Criteria:

  • Any serious medical condition including but not limited to uncontrolled hypertension, diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), renal failure, splenomegaly, leukemic features, active hemorrhage, or psychiatric illness that, in the investigator's opinion, places the patient at unacceptable risk and would prevent the subject from signing the informed consent form
  • Patients with ANY of the following risk factors:

    • Significant disease related symptoms (including significant B symptoms)
    • Blastoid variant histology
    • Pleomorphic variant histology
    • Ki-67 > 30%
    • Bulky tumors > 5 cm
    • Central nervous system (CNS) involvement at diagnosis
  • All patients must not have received any prior treatment for mantle cell lymphoma
  • Prior exposure to BTK inhibitor
  • Pregnant or breastfeeding females
  • Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded
  • All patients with history of central nervous system lymphoma
  • History of stroke or intracranial hemorrhage within 6 months prior to signing the consent
  • Currently active, clinically significant cardiovascular disease such as uncontrolled arrhythmia or any class 3 or 4 congestive heart failure as defined by the New York Heart Association Classification, or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization
  • Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, bradycardia (< 50 beats per minute [bpm]), or corrected QT (QTc) > 500 msec
  • Unable to swallow capsules, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
  • Requires concomitant anticoagulation with warfarin or equivalent vitamin K antagonist, active treatment for pulmonary embolism (PE)/ deep vein thrombosis (DVT) and persons with mechanical cardiac valves
  • Subject who received a strong cytochrome P450 (CYP) 3A inhibitor within 7 days prior to the first dose of ibrutinib or subject who requires continuous treatment with a strong CYP3A inhibitor
  • Subjects with chronic liver disease and hepatic impairment meeting Child-Pugh class C
  • Any uncontrolled active systemic infection
  • Major surgery within 4 weeks of first dose of study drug
  • Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
  • Recent infection requiring systemic treatment that was completed =< 14 days before the first dose of study drug
  • Known bleeding disorders (e.g., von Willebrand's disease or hemophilia)
  • Unresolved toxicities from prior anticancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version [v] 4.0), grade =< 1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia
  • Concurrent systemic immunosuppressant therapy within 21 days of the first dose of study drug

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03282396

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Contact: Michael Wang, MD, MS 713-792-2860
Contact: Jain Preetesh, MD, DM, PhD 713-792-2860

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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Luhua (Michael) Wang    713-792-2860      
Principal Investigator: Luhua (Michael) Wang         
Sub-Investigator: Preetesh Jain, MD, DM, PhD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Luhua (Michael) Wang M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT03282396    
Other Study ID Numbers: 2016-0914
NCI-2018-01045 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0914 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: September 13, 2017    Key Record Dates
Last Update Posted: June 18, 2020
Last Verified: June 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin