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

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
First received: November 24, 2011
Last updated: July 31, 2015
Last verified: March 2015
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.

Condition Intervention Phase
Adult Grade III Lymphomatoid Granulomatosis
Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
Intraocular Lymphoma
Nodal Marginal Zone Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Secondary Central Nervous System Non-Hodgkin Lymphoma
Small Intestinal Lymphoma
Splenic Marginal Zone Lymphoma
Testicular Lymphoma
Waldenstrom Macroglobulinemia
Drug: Akt Inhibitor MK2206
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of MK-2206 in Patients With Relapsed or Refractory Diffuse Large-B Cell Lymphoma

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • ORR (CR + PR) according to the 2007 International Cheson Response Criteria [ Time Frame: Up to 4 months ] [ Designated as safety issue: No ]
    Relying on a two-stage Simon's design.

Secondary Outcome Measures:
  • Duration of response [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Described in responding subjects using descriptive statistics (median, extreme values, etc.).

  • Overall survival [ Time Frame: From the date of inclusion to the date of death from any cause, assessed up to 4 years ] [ Designated as safety issue: No ]
    Analyzed using the Kaplan-Meier method. The median survival rates will be reported with a 95% confidence interval. Median follow-up will be calculated using the reverse Kaplan-Meier method.

  • Progression-free survival (PFS) [ Time Frame: From the date of inclusion to the date of first documented disease progression, relapse or death from any cause, assessed up to 4 years ] [ Designated as safety issue: No ]
    Analyzed using the Kaplan-Meier method. The median survival rates will be reported with a 95% confidence interval. Median follow-up will be calculated using the reverse Kaplan-Meier method.

  • Toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: December 2011
Study Completion Date: June 2014
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (Akt inhibitor MK2206)
Patients receive Akt inhibitor MK2206 PO once weekly on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Akt Inhibitor MK2206
Given PO
Other Name: MK2206
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies

Detailed Description:


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. (exploratory)

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01481129

Hopitaux de Paris
Vellefaux, Paris, France, 75010
Institut Bergonie Cancer Center
Bordeaux, France, 33076
Henri Mondor University-Hospital Center
Creteil, France, 94000
Hospital Claude Huriez Chru
Lille, France, 59037
Centre Leon Berard
Lyon, France, 69373
Institut Paoli Calmettes
Marseille, France, 13273
Hopital Saint Louis
Paris, France, 75010
Centre Hospitalier Lyon-Sud
Pierre Benite, France, 69310
Institut Gustave Roussy
Villejuif, France, 94805
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Herve Ghesquieres Centre Leon Berard
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01481129     History of Changes
Other Study ID Numbers: NCI-2012-00081, NCI-2012-00081, LEONB-ET-2011-041, 2011-001970-25, CDR0000716384, ET-2011-041, 9022
Study First Received: November 24, 2011
Last Updated: July 31, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Intraocular Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
Eye Neoplasms
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, T-Cell
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Plasma Cell
Precancerous Conditions
Vascular Diseases

ClinicalTrials.gov processed this record on November 27, 2015