Study of MK 2206 in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma

Inclusion Criteria:

* Patients with histologically confirmed diffuse large B-Cell lymphomas.
* Patients must have measurable disease.
* Subjects 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.
  * Prior treatment could include high dose chemotherapy with autologous stem-cell transplantation if patients had progressed ≥ 3 months after this treatment.
  * Salvage treatment, mobilization chemotherapy, high-dose chemotherapy and planned post-transplant therapy should be considered as one regimen
  * Relapsed or refractory patients who are candidate to high-dose chemotherapy and autologous or allogenic stem cell transplantation are not eligible.
* Patients must have discontinued all prior therapies for at least 5 times the t1/2 of prior anti-cancer therapies before study entry.
* Male or female patients, age ≥ 18 years.
* Life expectancy greater than 4 months.
* ECOG performance status ≤2.
* Patients must have normal organ and marrow function as defined below:

  * Absolute neutrophil count ≥ 1.5 x 109/L,
  * Platelet count ≥ 100 x 109/L or ≥75 x 109/L if the bone marrow is involved,
  * AST/ALT ≤ 2.5 x upper limit of normal (ULN) (or ≤ 5.0 x ULN if liver metastasis) direct bilirubin ≤ 1.5ULN
  * Calculated creatinine clearance (Cockcroft-Gault formula) of ≥ 50mL/min
* Patients must agree to use adequate double contraception
* Patients must be able to swallow whole tablets.
* Cardiovascular baseline QTcF≤ 450 msec (male) or QTcF≤470msec (female).
* Signed written informed consent document.
* Patients with French Social Security in compliance with the French law relating to biomedical research.

Exclusion Criteria:

* Tumor tissue sample not available for pathological review.
* Patients with others than Diffuse large B-Cell Lymphoma histology.
* Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
* Patients who have not recovered from adverse events grade \> 1 due to agents administered more than 4 weeks earlier.
* Patients who are receiving any other investigational agents.
* Patients with known CNS involvement should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the compliance to the study protocol.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 tablets.
* Patients with uncontrolled hyperglycemia
* Patients with 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 and breastfeeding women are excluded from this study.
* HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with MK-2206.
* Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption.
* Patients with clinically important history of liver disease, including viral or other hepatitis or cirrhosis.
* 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.
* Uncontrolled hypertension with resting SBP\>140 or resting DBP\>90mm Hg