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A Phase 2 Study of MK-2206 in Patients With Relapsed or Refractory Diffuse Large-B Cell Lymphoma

Phase 2
18 Years
Open (Enrolling)
Adult Grade III Lymphomatoid Granulomatosis, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Secondary Central Nervous System Non-Hodgkin Lymphoma, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Testicular Lymphoma, Waldenström Macroglobulinemia

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Trial Information

A Phase 2 Study of MK-2206 in Patients With Relapsed or Refractory Diffuse Large-B Cell Lymphoma


I. To evaluate the antitumor activity of Akt inhibitor MK2206 (MK2206) in terms of objective
response rate (ORR) at 4 months (complete response [CR], and partial response [PR]) as per
the 2007 International Cheson response criteria.


I. To evaluate the antitumor activity of MK2206 in terms of ORR at 4 months (CR, unconfirmed
complete response [CRu], and PR) as per the 1999 International Cheson response criteria.

II. To determine the duration of response, defined as the time from the date of the best
response to the date of progression.

III. To determine the progression-free survival and overall survival of these patients.

IV. To determine the safety of MK2206. V. To identify predictive biomarkers for treatment
outcome. (exploratory) VI. To conduct a pharmacodynamic study using FDG-PET scans.

OUTLINE: This a multicenter study.

Patients receive Akt inhibitor MK2206 orally (PO) once weekly on days 1, 8, 15, and 22.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

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

- The dominant masses should be from as disparate regions of the body as

- 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)


- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

ORR (CR + PR) according to the 2007 International Cheson Response Criteria

Outcome Description:

Relying on a two-stage Simon's design.

Outcome Time Frame:

Up to 4 months

Safety Issue:


Principal Investigator

Herve Ghesquieres

Investigator Role:

Principal Investigator

Investigator Affiliation:

Centre Leon Berard


United States: Food and Drug Administration

Study ID:




Start Date:

December 2011

Completion Date:

Related Keywords:

  • Adult Grade III Lymphomatoid Granulomatosis
  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Intraocular Lymphoma
  • Nodal Marginal Zone B-cell Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Secondary Central Nervous System Non-Hodgkin Lymphoma
  • Small Intestine Lymphoma
  • Splenic Marginal Zone Lymphoma
  • Testicular Lymphoma
  • Waldenström Macroglobulinemia
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphomatoid Granulomatosis
  • Waldenstrom Macroglobulinemia
  • Lymphoma, B-Cell
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Extranodal NK-T-Cell