Clinical trial NCT02242097: Ibrutinib After Intensive Induction in Treating Patients With Previously Untreated Mantle Cell Lymphoma
Official title: A Phase II Clinical Trial Evaluating Ibrutinib Maintenance Following Intensive Induction for Patients With Previously Untreated Mantle Cell Lymphoma (MCL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Janssen Scientific Affairs, LLC
name: National Cancer Institute (NCI)
First posted: 2014-09-16
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Determine the Progression-free Survival (PFS) Rate After 3 Years
timeFrame: Assessed at 3 years
Secondary outcomes:
measure: Incidence of Adverse Events, Defined According to the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.0
timeFrame: Up to 30 days after completion of study treatment, maximum 4 years post-first dose
measure: Rate of Conversion From Partial Response (PR) to Complete Response (CR)
timeFrame: Up to 4 years
measure: Overall Survival (OS) After 4 Years
timeFrame: Up to 4 years post-first dose
Other outcomes:
measure: Compare Minimum Residual Disease (MRD) Results Overtime by Polymerase Chain Reaction (PCR) and Correlate These With PFS and OS
timeFrame: Four time-points: baseline (pre-treatment), after 1 month and 6 months of treatment, and approximately 18-24 months post-first dose of treatment
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Lake Forest
country: United States
facility: Northwestern University- Lake Forest Hospital
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: Northwestern University
name: Barbara Pro, MD
role: PRINCIPAL_INVESTIGATOR
References: