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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01466868
• Date of registration: 28/10/2011
• Prospective Registration: Yes
• Primary sponsor: Centre Leon Berard
• Public title: Study of MK 2206 in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma AKTIL
• Scientific title: A Phase II Study of MK 2206 in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma
• Date of first enrolment: November 2011
• Target sample size: 22
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT01466868
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Philippe Cassier, MD
• Affiliation: Centre Leon Berard

• Name: Hervé Ghesquières, MD
• Affiliation: Centre Leon Berard, Lyon, France

Key inclusion & exclusion 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 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



Age minimum: 18 Years
Age maximum: 90 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Diffuse Large B Cell Lymphoma

Intervention(s)

Drug: MK2206

Primary Outcome(s)

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.]

Secondary Outcome(s)

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)]

safety profile [Time Frame: during the treatment and up to 3.5 years from the first inclusion]

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)]

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)]

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]

Secondary ID(s)

AKTIL

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute, France