Akt Inhibitor MK2206 in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Condition: Diffuse Large B Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: Akt Inhibitor MK2206; Laboratory Biomarker Analysis; Pharmacological Study
Intervention description: Given PO; Correlative studies; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well Akt inhibitor MK2206 works in treating patients with
      relapsed or refractory diffuse large B-cell lymphoma. Akt inhibitor MK2206 may stop the
      growth of cancer cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diffuse large B-cell lymphoma

               -  Relapsed or refractory disease

          -  Measurable disease

               -  At least one measurable lymph node mass that is > 1.5 cm in two perpendicular
                  dimensions and that has not been previously irradiated or has grown since
                  previous irradiation

                    -  Dominant lymph node masses include up to 6 nodal masses that are clearly
                       measurable in 2 perpendicular dimensions and > 1.5 cm in each dimension

                    -  Measurement may be by radiographic imaging

                    -  If there are lymph node masses in the mediastinum or pelvis larger than 1.5
                       cm in 2 perpendicular dimensions, they should always be chosen as dominant
                       masses

                    -  The dominant masses should be from as disparate regions of the body as
                       possible

               -  Measurable sites of disease are also extra-nodal sites such as splenic nodules
                  and hepatic nodules that are thought to contain lymphoma, and are greater than 1
                  cm in the longest transverse dimension

          -  Must have received at least two prior treatment lines; there is no maximal limit on
             the number of prior therapies

               -  Prior treatment must include CHOP (cyclophosphamide, doxorubicin, vincristine,
                  and prednisolone)-like chemotherapy in combination with rituximab

                    -  Rituximab used alone is not considered as a separate regimen

                    -  Salvage treatment, mobilization chemotherapy, high-dose chemotherapy, and
                       planned post-transplant therapy should be considered as one regimen

               -  Relapsed or refractory patients who are candidates for high-dose chemotherapy and
                  autologous or allogeneic stem cell transplantation are not eligible

          -  Tumor tissue sample must be available for pathological review

          -  No known CNS involvement

          -  ECOG performance status < 2 (Karnofsky > 60%)

          -  Life expectancy > 4 months

          -  Absolute neutrophil count >= 1,500/µL

          -  Platelets >= 100,000/µL (>= 75,000/µL if the bone marrow is involved)

          -  Total bilirubin =< 1.5 X institutional upper limit of normal (ULN)

          -  AST(SGOT)/ALT(SGPT) =< 2.5 X ULN

          -  Calculated creatinine clearance >= 50 mL/min

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Women of child-bearing potential and men must agree to use adequate contraception

          -  Must be able to swallow whole tablets

               -  Nasogastric or G-tube administration is not allowed

               -  Tablets must not be crushed or chewed

          -  Patients with French Social Security in compliance with the French law relating to
             biomedical research allowed

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to MK2206 tablets

          -  Hyperglycemia should be well controlled on oral agents

          -  Cardiovascular baseline QTcF =< 450 msec (male) or QTcF =< 470 msec (female)

          -  No 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

          -  No HIV-positive patients on combination antiretroviral therapy

          -  No patients with malabsorption syndrome or other condition that would interfere with
             intestinal absorption

          -  No patients with clinically important history of liver disease, including viral or
             other hepatitis or cirrhosis

          -  No prior history of malignancies other than lymphoma (except for basal cell or
             squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast)
             unless the subject has been free of the disease for >= 3 years

          -  Must have recovered from adverse events due to agents administered more than 4 weeks
             earlier

          -  Patients must have discontinued all prior therapies for at least 5 times the half-life
             of all prior anticancer therapies before study entry

          -  Prior treatment could include high-dose chemotherapy with autologous stem-cell
             transplantation if patients had progressed >= 3 months after this treatment

          -  No chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin
             C)

          -  Patients must not be receiving any other investigational agents

          -  No other investigational or commercial agents or therapies may be administered with
             the intent to treat the patient's malignancy

          -  No concurrent radiotherapy