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

This study is currently recruiting participants.
Verified July 2012 by Centre Leon Berard

First Received on October 28, 2011.  
Last Updated on July 20, 2012  
History of Changes
This Clinical Trial Sponsored By: Centre Leon Berard
Collaborator: National Cancer Institute, France
Information provided by (Responsible Party): Centre Leon Berard
ClinicalTrials.gov Identifier: NCT01466868
 

Purpose for Clinical Trial

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.

Condition Study Intervention Clinical Trial Phase
Diffuse Large B Cell Lymphoma Drug: MK2206 Phase 2

Study Type: Study Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics:
Lymphoma

U.S. FDA Resources

Further study details as provided by Centre Leon Berard:

Primary Outcome Measures For Clinical Trial:

  • 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.

Secondary Outcome Measures For Clinical Trial:

  • 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.

Estimated Enrollment: 51
Study Start Date: November 2011
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)

Arms

Assigned Study Interventions

Experimental: MK2206

Treatment is started the day after registration (day 1)until progression according to Cheson international response criteria or documented toxicity.
Drug: MK2206

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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 rece

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