Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01258998
First received: December 10, 2010
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

The goal of this clinical research study is to learn if Akt inhibitor MK2206 can help to control Hodgkin and non-Hodgkin lymphoma. The safety of this drug will also be studied.


Condition Intervention Phase
Adult Grade III Lymphomatoid Granulomatosis
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Hairy Cell Leukemia
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Waldenström Macroglobulinemia
Drug: Akt inhibitor MK2206
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: PHASE II STUDY OF MK-2206 IN PATIENTS WITH RELAPSED LYMPHOMA

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • ORR [ Time Frame: 4 months ] [ Designated as safety issue: No ]
    Objective response (OR) rate along with its 95% confidence interval (CI) will be estimated for each patient cohort. Logistic regression will be utilized to assess the effect of patient demographic factors on OR.


Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 30 days ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.

  • Duration of response [ Time Frame: From the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 30 days ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.

  • Overall survival [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]
    Will be estimated using the Kaplan-Meier method. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model will be used to include multiple covariates in the time-to-event analysis.

  • Toxicities assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
    Toxicity data will be summarized by frequency tables. The association between both type and severity of toxicity and the treatment groups will be evaluated. No formal statistical testing will be performed on these summary data.


Estimated Enrollment: 150
Study Start Date: December 2010
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (Akt inhibitor MK2206)
Patients receive Akt inhibitor MK2206 PO once weekly. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Drug: Akt inhibitor MK2206
Given PO
Other Name: MK2206
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the objective response rate (ORR) of MK-2206 (Akt inhibitor MK2206) in patients with relapsed/refractory lymphoma.

SECONDARY OBJECTIVES:

I. Assess the progression free survival (PFS) of MK-2206 in patients with relapsed/refractory lymphoma II. Assess the safety and tolerability of MK-2206 monotherapy III. Examine pretreatment pAkt protein expression by immunohistochemistry, and correlate the results with treatment response.

IV. Examine the effect of therapy on serum cytokines and chemokines that regulate the tumor-promoting inflammatory process and/or immunity in patients with relapsed/refractory lymphoma, and correlate the results with treatment response.

OUTLINE:

Patients receive Akt inhibitor MK2206 orally (PO) once weekly. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) (small lymphocytic lymphoma may be included)
  • Relapsed or refractory after at least one regimen and with no curative option with conventional therapy
  • Bidimensionally measurable disease (at least 2 cm)
  • No evidence of cerebral or meningeal involvement by lymphoma
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
  • Signed informed consent form prior to enrollment
  • Women of childbearing potential and men must use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a women become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately

Exclusion Criteria:

  • Burkitt's lymphoma, lymphoblastic lymphoma, chronic lymphocytic leukemia and cutaneous T-cell lymphoma
  • Chemotherapy or radiation therapy or other investigational agents within 3 weeks prior to entering the study unless there is clear evidence of progression of disease and toxicity from previous treatment has resolved in which case study entry may be within 1 week of last treatment
  • Previous radioimmunotherapy within 12 weeks
  • Patients with known HIV infection must not have CD4 cells < 400/mm3 and who must not have a prior AIDS-defining diagnosis and cannot be on antiretroviral therapy for HIV
  • Known active viral hepatitis
  • Any serious active disease or co-morbid condition, which in the opinion of the principal investigator, will interfere with the safety or with compliance with the study
  • Absolute neutrophil count < 1.5 x 10^9/L
  • Platelets < 75 x 10^9/L
  • Total bilirubin > 1.5 x ULN (> 3 x upper limit of normal [ULN] for patients with liver involvement)
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 2.5 x ULN (> 5 x ULN for patients with liver involvement)
  • Serum creatinine > 2 x ULN
  • Hemoglobin (Hb)A1C > 8%
  • Patients receiving any medications or substances that are inhibitors of CYP 450 3A4 are ineligible
  • Patients with diabetes or in risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial
  • Cardiovascular: baseline QTcF > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study
  • Significant heart block or baseline bradycardia < 50bpm due to cardiac disease
  • Patients who are pregnant or breastfeeding
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01258998

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: Yasuhiro Oki M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01258998     History of Changes
Other Study ID Numbers: NCI-2012-02890, NCI-2012-02890, 2010‐0261, 8728, P30CA016672, N01CM00039
Study First Received: December 10, 2010
Last Updated: January 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Hairy Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Mantle-Cell
Leukemia, Large Granular Lymphocytic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders

ClinicalTrials.gov processed this record on April 17, 2014