Ibrutinib After Intensive Induction in Treating Patients With Previously Untreated Mantle Cell Lymphoma

NCT ID: NCT02242097

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-12
• Study Completion Date: 2025-01-31

Brief Summary

This study is being done to see whether or not a drug called ibrutinib can be given to patients with mantle cell lymphoma (MCL) as maintenance therapy after induction chemotherapy. This drug blocks an enzyme that affects how the lymphocytes grow and survive. The investigators hope to learn how safe and effective ibrutinib is for treating patients with MCL after responding to induction chemotherapy.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the progression-free survival (PFS) rate after 3 years.

SECONDARY OBJECTIVES:

I. Assess toxicity. II. Determine rates of conversion from partial response (PR) to complete response (CR).

III. Determine median overall survival (OS) after 4 years.

TERTIARY OBJECTIVES:

I. Compare minimal residual disease (MRD) results overtime by polymerase chain reaction (PCR) and correlate these with PFS and OS.

OUTLINE:

Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days for up to 4 years in the absence of disease progression, unacceptable toxicity or patient preference.

After completion of study treatment, patients who completed 4 years of treatment are followed up at 30 days. Patients who did not complete 4 years of treatment are followed up for up to 4 years post-first dose of treatment (every 3 months for 2 years and then every 6 months for 4 years).

Conditions

Contiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Stage I Mantle Cell Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Mantle Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (ibrutinib)

Patients receive ibrutinib orally PO QD on days 1-28. Courses repeat every 28 days for up to 4 years in the absence of disease progression, unacceptable toxicity, or patient preference.

Group Type: EXPERIMENTAL

ibrutinib

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

ibrutinib

Given PO

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Bruton's tyrosine kinase inhibitor PCI-32765; BTK inhibitor PCI-32765; CRA-032765; Imbruvica; PCI-32765

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically confirmed mantle cell lymphoma (MCL)

• Please note: Measurable disease is not required, but will be followed if it exists
• Patients must have received 4 or more cycles of one of the following prior systemic induction chemotherapy regimens:

• Rituximab, cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), prednisone (R-CHOP) (with or without alternating rituximab, dexamethasone, cytarabine [ara-c], cisplatin [platinum] [R-DHAP]) with or without autologous (auto) stem cell transplant (SCT)
• Hyper-cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride (adriamycin), dexamethasone (CVAD) with or without auto SCT
• Bendamustine + rituximab with or without auto SCT

• Please note:

• Patients who received combinations of the above regimens are not eligible for enrollment
• At the time of registration, patients must be at least 14 days out from last dose of cytotoxic chemotherapy, but no more than 90 days; if a patient underwent auto SCT, he/she must demonstrate engraftment (per treating investigator's discretion) and must meet all other hematological requirements as outlined below
• Patients must have achieved a response to induction chemotherapy (either CR or PR by Cheson 2007 criteria) and be without known progression
• Patients may have received prior radiotherapy
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count (ANC) >= 1000/mm^3, independent of growth factor support
• Platelets >= 100,000/mm^3, or >= 50,000 in cases of ongoing bone marrow involvement (in either case, these must be independent of transfusion support)
• Total bilirubin =< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT]) =< 3 x ULN
• Creatinine clearance >= 25 ml/min
• Please note: Patients who do not meet the above criteria because of Gilbert's Syndrome are still eligible
• Women of child-bearing potential (WOCBP) 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 (see timelines below for women and men); in addition, men must agree not to donate sperm during and after study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

• NOTE: For female patients, these restrictions apply for 1 month after the last dose of study drug; for male patients, these restrictions apply for 3 months after the last dose of study drug
• NOTE: A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• Female patients must have a negative pregnancy test (blood or urine) within 28 days prior to registration
• Patients must be willing and able to avoid consuming food and beverages containing grapefruit or Seville oranges while on ibrutinib study therapy
• Patients must have the ability to understand and the willingness to sign a written informed consent prior to registration on study

Exclusion Criteria

• Patients who have received >= 7 days of prior ibrutinib or any prior treatment with another Bruton tyrosine kinase (BTK) inhibitor are not eligible
• Patients receiving ongoing treatment with any other investigational agents are not eligible
• Patients receiving live/attenuated vaccinations within 4 weeks prior to registration are not eligible
• Patients with a known central nervous system (CNS) involvement of lymphoma are not eligible (CNS staging not required)
• Patients who have undergone major surgery within 4 weeks prior to registration are not eligible
• Patients diagnosed or treated for malignancy other than MCL are not eligible unless they meet one of the following exceptions:

• Malignancy treated with curative intent and with no known active disease present for >= 3 years before registration and felt to be at low risk for recurrence by the treating physician
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated cervical carcinoma in situ without evidence of disease
• Patients with a history of stroke or intracranial hemorrhage within 6 months prior to registration are not eligible
• Patients who require anticoagulation with warfarin or equivalent vitamin K antagonists are not eligible
• Patients who require chronic treatment with strong cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) inhibitors are not eligible

• NOTE: Patients who are currently on treatment with strong CYP3A4/5 inhibitors may be eligible if they are able to be switched to an alternative therapy that is not a strong CYP3A4/5 inhibitor prior to registration on study
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib are not eligible
• Patients with uncontrolled intercurrent illness including, but not limited to, any of the following are not eligible:

• Ongoing or active systemic infection
• Symptomatic congestive heart failure
• Myocardial infarction within 6 months prior to registration
• Unstable angina pectoris
• Uncontrolled or symptomatic cardiac arrhythmias
• Any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• Psychiatric illness/social situations that would limit compliance with study requirements
• Patients who have any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at risk are not eligible
• Patients with a known human immunodeficiency virus (HIV) infection are not eligible (HIV testing not required)
• Patients with a known John Cunningham (JC) virus infection and/or progressive multifocal leukoencephalopathy (PML) are not eligible
• Patients with clinically active hepatitis A, B, or C infections are not eligible
• Female patients who are pregnant and/or lactating are not eligible

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Barbara Pro, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

Northwestern University- Lake Forest Hospital

Lake Forest, Illinois, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

Karmali R, Abramson JS, Stephens DM, Barnes J, Winter JN, Ma S, Gao J, Kaplan J, Petrich AM, Hochberg E, Takvorian T, Mi X, Nelson V, Gordon LI, Pro B. Ibrutinib maintenance after frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023 Dec 12;7(23):7361-7368. doi: 10.1182/bloodadvances.2023011271.

Reference Type: DERIVED

PMID: 37756532 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2014-01777

Identifier Type: REGISTRY

Identifier Source: secondary_id

PCI-32765MCL2003

Identifier Type: -

Identifier Source: secondary_id

STU00098385

Identifier Type: -

Identifier Source: secondary_id

NU 14H06

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA060553

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NU 14H06

Identifier Type: -

Identifier Source: org_study_id