Akt Inhibitor MK2206 in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

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 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 = = 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 = = 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