Obinutuzumab in Combination With Ibrutinib in Treating Patients With Relapsed Mantle Cell Lymphoma
Condition: Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: Ibrutinib; Obinutuzumab
Intervention description: Given PO; Given IV
Intervention MeSH terms: Obinutuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well obinutuzumab works in combination with ibrutinib in
      treating patients with mantle cell lymphoma that has returned (relapsed) or that does not
      respond to treatment (refractory). Obinutuzumab binds to a protein called cluster of
      differentiation (CD)20, which is found on B cells and some types of leukemia and lymphoma
      cells and help the immune system kill cancer cells. Ibrutinib blocks a protein called
      Bruton's tyrosine kinase (BTK), which may help keep cancer cells from growing. Giving
      obinutuzumab in combination with ibrutinib may kill more cancer cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must have a diagnosis of relapsed or refractory mantle cell lymphoma as
             follows:

               -  Diagnosis of mantle cell lymphoma (MCL) must include morphology and expression of
                  either cyclin D1 in association with other relevant markers (eg, CD19, CD20, CD5)
                  or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ
                  hybridization (FISH), or polymerase chain reaction (PCR)

               -  Relapsed or refractory disease is defined as no response or progressive disease
                  to prior treatment if the prior treatment comprised any of the following:

                    -  1 regimen containing an anti-CD20 antibody administered for >= 2 doses,
                       and/or

                    -  >= 1 regimen containing 1 cytotoxic agent (e.g., bendamustine, chlorambucil,
                       cyclophosphamide, cytarabine, doxorubicin) administered for 2 cycles

          -  At least 1 measurable site of disease according to Revised Response Criteria for
             Malignant Lymphoma (Cheson Criteria); the site of disease must be greater than 1.5 cm
             in the long axis regardless of short axis measurement or greater than 1.0 cm in the
             short axis regardless of long axis measurement, and clearly measurable in 2
             perpendicular dimensions

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)

          -  Absolute neutrophil count (ANC) >= 1.0 K/cu mm; for subjects with ANC < 1.0 K/cu mm
             due to significant marrow involvement by MCL, ANC must be > .5 K/cu mm

          -  Platelets (plt) >= 50 K/cu mm; for subjects with plt < 50 K/cu mm due to significant
             marrow involvement by MCL, plt must be > 25 K/cu mm

          -  Total bilirubin =< 2.5 X institutional limits

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 X institutional upper limit of normal

          -  Creatinine =< 2

          -  Women of childbearing potential and men who are sexually active must be practicing a
             highly effective method of birth control during and after the study consistent with
             local regulations regarding the use of birth control methods for subjects
             participating in clinical trials; men must agree to not donate sperm during and after
             the study; for females, these restrictions apply for 18 months after last dose of
             obinutuzumab, or 1 month after the last dose of ibrutinib, whichever is later; for
             males, these restrictions apply for 180 days after the last dose of obinutuzumab or 3
             months after the last dose of ibrutinib, whichever is later

          -  Women of childbearing potential must have a negative serum (beta-human chorionic
             gonadotropin [beta-hCG]) or urine pregnancy test at screening; women who are pregnant
             or breastfeeding are ineligible for this study

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Major surgery within 4 weeks of drug administration

          -  Diagnosed or treated for malignancy other than MCL, except:

               -  Malignancy treated with curative intent and with no known active disease present
                  for >= 2 years

               -  Adequately treated non-melanoma skin cancer or melanoma in situ without evidence
                  of disease

               -  Adequately treated cervical carcinoma in situ without evidence of disease

               -  Asymptomatic prostate cancer managed with "active surveillance"

               -  Localized prostate cancer treated with definitive treatment including radiation
                  or surgery. Patients on adjuvant hormone deprivation treatment such as lupron are
                  eligible. Patients with known metastatic disease are ineligible

          -  History of stroke or intracranial hemorrhage within 6 months prior to randomization

          -  Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg,
             phenprocoumon)

          -  Vaccinated with live, attenuated vaccines within 4 weeks of randomization

          -  Requires treatment with strong cytochrome P450 3A (CYP3A) inhibitors

          -  Subjects who have had standard cytotoxic chemotherapy or radiotherapy within 3 weeks
             prior to entering the study or those whose adverse events due to agents administered
             more than 3 weeks earlier have not recovered to =< grade 1; this excludes alopecia and
             hematologic adverse events

          -  Subjects who have had radiotherapy within 2 weeks prior to entering the study or those
             whose adverse events due to radiotherapy more than 2 weeks earlier have not recovered
             to =< grade 1

          -  Subjects who have received investigational or approved oral or "targeted" agents (such
             as spleen tyrosine kinase [SYK], phosphatidylinositol 3 kinase [PI3K], B-cell chronic
             lymphocytic leukemia [CLL]/lymphoma 2 [bcl-2], BTK inhibitors) or lenalidomide within
             1 week prior to entering the study or those whose adverse events due to agents
             administered more than 1 week earlier have not recovered to =< grade 1; this excludes
             hematologic adverse events; the exception is subjects who are currently receiving
             ibrutinib (for < 14 days). In this case, ibrutinib can be continued

          -  Subjects who have received monoclonal antibodies (such as Rituxan) within 1 week prior
             to entering the study or those whose adverse events due to agents administered more
             than 1 week earlier have not recovered to =< grade 1; this excludes hematologic
             adverse events

          -  Subjects who are actively receiving any other investigational agents

          -  History of severe allergic reactions attributed to compounds of similar chemical or
             biologic composition as obinutuzumab or ibrutinib or other agents used in the study

          -  Uncontrolled intercurrent 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

          -  Pregnant or lactating women are excluded from this study

          -  Known history of human immunodeficiency virus (HIV) or active hepatitis C

          -  Virus or active hepatitis B virus infection; patients who are hepatitis B core
             antibody (HBcAb) positive may be eligible as long as there is no evidence of active
             infection with negative hepatitis B (Hep B) by polymerase chain reaction (PCR); in
             this case, Hep B PCR must be monitored monthly

          -  Any uncontrolled active systemic infection requiring intravenous (IV) antibiotics

          -  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 undue
             risk

          -  Patients previously treated with ibrutinib > 14 days are ineligible; no drug
             intervention or cessation is required for patients already receiving ibrutinib prior
             to initiation of on-study therapy

          -  Active graft versus (vs.) host disease (GVHD)

          -  Ongoing glucocorticoids (prednisone > 10 mg daily, or equivalent); higher doses (> 10
             mg daily) are permitted for up to 5 days to help control disease related symptoms