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

NCT01466868 | Terminated Phase 2 DMC

• 1 other identifier: AKTIL
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Diffuse Large B Cell Lymphoma

Keywords

Diffuse Large B cell Lymphoma; AKT; MK 2206; objective response rate; progression free survival; overall survival; safety

Outcome Measures

Primary Outcomes (1)

• evaluation of the antitumor activity of MK-2206 in terms of objective response rate (ORR).

  the objective response rate (ORR) is measured as per 2007 Cheson international response criteria.

  4 months after the first day of treatment.

Secondary Outcomes (5)

• safety profile

  during the treatment and up to 3.5 years from the first inclusion

• overall survival

  from the date of inclusion to the date of death from any cause (up to 3.5 years from the first inclusion)

• progression-free survival

  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)

• duration of response

  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)

• evaluation of the antitumor activity of MK-2206 in terms of objective response rate (ORR).

  4 months after the first day of treatment

Study Arms (1)

MK2206

EXPERIMENTAL

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

Drug: MK2206

Interventions

MK2206 DRUG

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.

MK2206

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 receiving any other investigational agents.
• Patients with known CNS involvement should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the compliance to the study protocol.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 tablets.
• Patients with uncontrolled hyperglycemia
• Patients with 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.
• Pregnant and breastfeeding women are excluded from this study.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with MK-2206.
• Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption.
• Patients with clinically important history of liver disease, including viral or other hepatitis or cirrhosis.
• 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.
• Uncontrolled hypertension with resting SBP\>140 or resting DBP\>90mm Hg

Sponsors & Collaborators

• Centre Leon Berard: lead
• National Cancer Institute, France: collaborator

Study Sites (13)

Institut Bergonié

Bordeaux, 33000, France

Location

Centre Henri Mondor

Créteil, France

Location

CHRU

Lille, France

Location

Centre Leon Berard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, 13000, France

Location

CHU St Eloi

Montpellier, France

Location

CHU

Nancy, France

Location

CHU de Nantes

Nantes, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

Hôpital Necker

Paris, 75014, France

Location

Centre Hospitalier LYON SUD

Pierre-Bénite, France

Location

Centre Henri Becquerel

Rouen, France

Location

Institut Gustave Roussy

Villejuif, France

Location

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MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

MK 2206

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Hervé Ghesquières, MD

  Centre Leon Berard, Lyon, France

  PRINCIPAL INVESTIGATOR

• Philippe Cassier, MD

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2011
• First Posted: November 8, 2011
• Study Start: November 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: June 1, 2014
• Last Updated: July 10, 2014

Record last verified: 2014-07

Locations

FR (13)