Study of MK 2206 in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma (AKTIL)
The purpose of this study is to evaluate the antitumor efficacy and the safety of MK 2206 in patients with relapsed or refractory diffuse large B cell lymphoma.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of MK 2206 in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma|
- evaluation of the antitumor activity of MK-2206 in terms of objective response rate (ORR). [ Time Frame: 4 months after the first day of treatment. ] [ Designated as safety issue: No ]the objective response rate (ORR) is measured as per 2007 Cheson international response criteria.
- safety profile [ Time Frame: during the treatment and up to 3.5 years from the first inclusion ] [ Designated as safety issue: Yes ]safety profile is characterized by type, frequency and seriousness of the toxicities showed by patients and graded using CTCAE-V04.
- overall survival [ Time Frame: from the date of inclusion to the date of death from any cause (up to 3.5 years from the first inclusion) ] [ Designated as safety issue: No ]
- progression-free survival [ Time Frame: from the date of inclusion to the date of event defined as the first documented disease progression or death from any cause (up to 3.5 years from the first inclusion) ] [ Designated as safety issue: No ]
- duration of response [ Time Frame: from the time of first documented response (complete response or partial response) until the first documented disease progression or death due to underlying cancer (up to 3.5 years from the first inclusion) ] [ Designated as safety issue: No ]
- evaluation of the antitumor activity of MK-2206 in terms of objective response rate (ORR). [ Time Frame: 4 months after the first day of treatment ] [ Designated as safety issue: No ]the objective response rate (ORR) is measured as per 1999 Cheson international response criteria.
|Study Start Date:||November 2011|
|Estimated Study Completion Date:||May 2014|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Treatment is started the day after registration (day 1)until progression according to Cheson international response criteria or documented toxicity.
Treatment will be administered orally once weekly, 2 hours before or after a meal, at day 1, 8, 15, 22 over a 28 day cycle period.
The starting dose level is 200 mg. 2 dose reduction are allowed (135 mg and 90 mg)in case of documented toxicity according to the specific algorithms.
Diffuse Large B-cell Lymphoma (DLBCL) is the most frequent subtype of Non-Hodgkin lymphoma (NHL) around the world, in all age groups.
DLBCL is a curable disease and combination of monoclonal antibody against CD20 (rituximab) with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) regimen have improved the prognosis of patients with a 20% increase of the cure rate. For the remaining patients who are not in complete response and/or who relapse after first line therapy, the possibility of cure is dramatically reduced.
As PI3K/AKT/mTOR pathway regulates the expression of cyclin D1, c-Myc and Stat3 proteins, which are involved in the pathogenesis of DLBCL HL), this signalling axis is an emerging therapeutic target for treatment of DLBCL.
One study has shown that the level of p-Akt is an adverse prognostic feature in DLBCL and is found in 52% of tumors samples from DLBCL patients.
Given the fact that AKT is overactivated in about to 52% of DLBCL and is considered as a poor prognosis factor, we postulate that targeting AKT in DLBCL may be an interesting therapeutic strategy.
MK-2206 is an orally selective allosteric inhibitor of AKT developed by MERCK currently highlighted as a promising therapeutic option for cancer patients and under clinical development in several Phase 1 trials.
Therefore, we propose to conduct a Phase II study using a two-stage Simon's design with objective response rate (ORR) as the primary endpoint.
|Bordeaux, France, 33000|
|Centre Henri Mondor|
|Centre Leon Berard|
|Institut Paoli Calmettes|
|Marseille, France, 13000|
|CHU St Eloi|
|CHU de Nantes|
|Paris, France, 75014|
|Paris, France, 75010|
|Centre Hospitalier LYON SUD|
|Pierre Bénite, France|
|Centre Henri Becquerel|
|Institut Gustave Roussy|
|Principal Investigator:||Hervé Ghesquières, MD||Centre Leon Berard, Lyon, France|
|Principal Investigator:||Philippe Cassier, MD||Centre Leon Berard|