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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01481129
First received: November 24, 2011
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

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 B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Secondary Central Nervous System Non-Hodgkin Lymphoma
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Testicular Lymphoma
Waldenström Macroglobulinemia
Drug: Akt inhibitor MK2206
Other: pharmacological study
Other: laboratory biomarker analysis
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:
  • 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.

  • 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.

  • 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.).

  • 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 ]

Estimated Enrollment: 51
Study Start Date: December 2011
Estimated Primary Completion Date: May 2015 (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: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

  Eligibility

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

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

Locations
France
Hopitaux de Paris Recruiting
Vellefaux, Paris, France, 75010
Contact: Richard Delarue    33 1 44 49 52 96    richard.delarue@nck.ap-hop-paris.fr   
Principal Investigator: Richard Delarue         
Institut Bergonie Cancer Center Recruiting
Bordeaux, France, 33000
Contact: Pierre Soubeyran    33 5 56 33 33 33    Soubeyran_p@bergonie.org   
Principal Investigator: Pierre Soubeyran         
Henri Mondor University-Hospital Center Recruiting
Creteil, France, 94000
Contact: Corinne Haioun    33 1 49 81 20 51    corinne.haioun@hmn.aphp.fr   
Principal Investigator: Corinne Haioun         
Hospital Claude Huriez Chru Recruiting
Lille, France, 59037
Contact: Herve Ghesquieres    33 4 78 78 26 84    ghesquie@lyon.fnclcc.fr   
Principal Investigator: Herve Ghesquieres         
Centre Leon Berard Recruiting
Lyon, France, 69373
Contact: Herve Ghesquieres    33-4-78-78-26-84    ghesquie@lyon.fnclcc.fr   
Principal Investigator: Herve Ghesquieres         
Institut Paoli Calmettes Recruiting
Marseille, France, 13273
Contact: Herve Ghesquieres       ghesquie@lyon.fnclcc.fr   
Principal Investigator: Herve Ghesquieres         
Hopital Saint Louis Recruiting
Paris, France, 75010
Contact: Catherine G. Thieblemont    33 1 42 49 98 37    catherine.thieblemont@sls.ap-hop-paris.fr   
Principal Investigator: Catherine G. Thieblemont         
Centre Hospitalier Lyon-Sud Recruiting
Pierre Benite, France, 69310
Contact: Bertrand Coiffier    33 4 78 86 43 02    bertrand.coiffier@chu-lyon.fr   
Principal Investigator: Bertrand Coiffier         
Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Contact: Vincent Ribrag    33 1 42 11 43 47    vincent.ribrag@igr.fr   
Principal Investigator: Vincent Ribrag         
Sponsors and Collaborators
Investigators
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: September 16, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 01, 2014