Selumetinib in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
Condition: Recurrent Adult Diffuse Large Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Intervention: Laboratory Biomarker Analysis; Selumetinib
Intervention description: Correlative studies; Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II clinical trial is studying how well selumetinib works in treating patients with
      relapsed or refractory diffuse large B-cell lymphoma. Selumetinib may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care, with the understanding that consent may be withdrawn
             by the subject at any time without prejudice to future medical care

          -  Relapsed or refractory diffuse large B-cell lymphoma (transformed large cell lymphomas
             are allowed to enroll)

          -  Patients must have received at least one previous therapeutic regimen, and no more
             than 6 previous therapeutic regimens

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Life expectancy > 3 months

          -  No chemotherapy, radiation therapy, immunotherapy, or experimental anticancer therapy
             within 28 days before beginning study treatment

          -  Human immunodeficiency virus (HIV)-positive patients are eligible if: the cluster of
             differentiation (CD)4 count is > 400, have no acquired immune deficiency syndrome
             (AIDS)-defining illnesses (other than non-Hodgkin lymphoma [NHL]), and they are not
             taking combination antiretroviral therapy (cART) at the time of study entry that would
             interfere with cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP4503A4)

          -  No other active infection

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control, or abstinence) prior to study entry, for
             the duration of study participation, and for 4 weeks after dosing with AZD6244
             hyd-sulfate ceases; women of child-bearing potential must have a negative pregnancy
             test prior to entry; should a woman become pregnant or suspect she is pregnant while
             she or her partner participating in this study, the patient should inform her treating
             physician immediately; please note that the AZD6244 hyd-sulfate manufacturer
             recommends that adequate contraception for male patients should be used for 16 weeks
             post-last dose due to sperm life cycle

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             the mother is treated with AZD6244 hyd-sulfate

          -  Patients may have received prior autologous, but not prior allogeneic stem cell
             transplant; however, patients who are eligible for potentially curative treatment with
             bone marrow transplant should not be entered on this investigational trial, unless
             they refuse the transplant option (or are not eligible for transplantation)

        Exclusion Criteria:

          -  Any prior exposure to mitogen-activated protein kinase kinase (MEK), Ras, or v-raf
             murine sarcoma 3611 viral oncogene homolog (Raf) inhibitors

          -  Patients with any active central nervous system (CNS) involvement by lymphoma are
             excluded

          -  Patients that are taking drugs that alter CYP450 3A4 (or cannot be changed to drugs
             that do not alter CYP450 3A4) are excluded

          -  Cardiac conditions as follows:

               -  Uncontrolled hypertension (blood pressure [BP] >= 150/95 despite optimal therapy)

               -  Heart failure New York Heart Association (NYHA) class II or above

               -  Prior or current cardiomyopathy

               -  Baseline left ventricular ejection fraction (LVEF) =< 50%

               -  Atrial fibrillation with heart rate > 100 beats per minute (bpm)

               -  Unstable ischemic heart disease (myocardial infarction [MI] within 6 months prior
                  to starting treatment, or angina requiring use of nitrates more than once weekly)

               -  Patients are excluded if there is corrected QT (QTc) interval > 450 msecs or
                  other factors that increase the risk of QT prolongation or arrhythmic events
                  (e.g., heart failure, hypokalemia, family history of long QT interval syndrome)

               -  Patients are excluded if they are taking any drugs that may significantly prolong
                  the QTc; these drugs are prohibited during the study; if the patient is taking
                  one or more of these medications, they may enroll if all pertinent medications
                  are stopped with the associated "wash out" periods

          -  Absolute neutrophil count (ANC) < 1.5 x 10^9/L (1500 per mm^3)

          -  Platelets < 100 x 10^9/L

          -  Hemoglobin (Hgb) < 8.0 g/dL

          -  Serum bilirubin >= 1.5 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) or
             alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) >= 2.5 x
             ULN (>= 5 ULN in presence of liver metastases)

          -  There should be a minimum of a 1 month wash-out interval from another investigational
             product to AZD6244 hyd-sulfate dosing start plus recovery from side effects of
             investigational product

          -  There should be a minimum of a 1 month wash-out interval from the end of previous
             systemic treatment and radiotherapy

          -  Patients are excluded if there is a history of a serious medical or psychiatric
             illness likely to interfere with participation in this clinical study

          -  Patients may not have recent history of refractory nausea and vomiting, chronic
             gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel
             resection that would preclude adequate absorption