Skip to main content
OpenTrials
Completed

NCT Number: NCT01258998

Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma

This phase II clinical trial studies how well Akt inhibitor MK2206 works in treating patients with relapsed lymphoma. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma B-cell Adult Acute Lymphoblastic Leukemia B-cell Chronic Lymphocytic Leukemia Blood Protein Disorders Cardiovascular Diseases Chronic Disease Cutaneous B-cell Non-Hodgkin Lymphoma Disease Attributes Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Eye Neoplasms Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Hepatosplenic T-cell Lymphoma Hodgkin Disease Immune System Diseases Immunoblastic Lymphadenopathy Immunoproliferative Disorders Intraocular Lymphoma Leukemia Leukemia, B-Cell Leukemia, Hairy Cell Leukemia, Large Granular Lymphocytic Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Leukemia, T-Cell Lymphadenopathy Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Extranodal NK-T-Cell Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Anaplastic Lymphoma, Large-Cell, Immunoblastic Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoma, T-Cell, Peripheral Lymphoproliferative Disorders Mycosis Fungoides Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Plasma Cell Nodal Marginal Zone B-cell Lymphoma Noncutaneous Extranodal Lymphoma Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Peripheral T-cell Lymphoma Precursor Cell Lymphoblastic Leukemia-Lymphoma Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Recurrent Adult Acute Lymphoblastic Leukemia 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 Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin 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 Sezary Syndrome Small Intestine Lymphoma Splenic Marginal Zone Lymphoma T-cell Adult Acute Lymphoblastic Leukemia T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Vascular Diseases Waldenstrom Macroglobulinemia Waldenström Macroglobulinemia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

About this study

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 phosphorylated v-akt murine thymoma viral oncogene homolog 1 (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.

After completion of study treatment, patients are followed up for 30 days.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 immunodeficiency virus (HIV) infection must not have cluster of differentiation (CD)4 cells < 400/mm^3 and who must not have a prior acquired immunodeficiency syndrome (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 upper limit of normal (ULN) (> 3 x 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 cytochrome P450 family 3, subfamily A, polypeptide 4 (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 Fredericia corrected QT interval (QTcF) > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study
  • Significant heart block or baseline bradycardia < 50 beats per minute (bpm) due to cardiac disease
  • Patients who are pregnant or breastfeeding

Treatment and study plan

Akt Inhibitor MK2206

Drug

Given PO

Other names: MK2206

laboratory biomarker analysis

Other

Correlative studies

Primary outcomes

  1. Objective Response Rate (ORR)

    Time frame: 4 months

    Complete Response (CR) Disappearance of all evidence of disease(a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative (b) Variably FDG-avid or PET negative; regression to normal size on CT Not palpable, nodules disappeared Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immuno histochemistry should be negative.

    Partial Response (PR) Regression of measurable disease and no new sites, 50% decrease in , sum of the product of the diameters SPD of up to 6 largest dominant masses; no increase in size of other nodes(a) FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site (b) Variably FDG-avid or PET negative; regression on CT, 50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen, Irrelevant if positive prior to therapy; cell type should be specified.

Secondary outcomes

  1. Progression-free Survival

    Time frame: From treatment start date until the date of first documented progression or date of death from any cause, whichever came first.

    Kaplan-Meier method was used. The log-rank test was performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model was used to include multiple covariates in the time-to-event analysis.

  2. Duration of Response

    Time frame: From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.

    Kaplan-Meier method was used. The log-rank test was performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model was used to include multiple covariates in the time-to-event analysis.

  3. Overall Survival

    Time frame: From the start of treatment to death or 30 days after removal from the study whichever occurs first

    Number of surviving participants without disease progression or death for any reason at one year post treatment. Kaplan-Meier method was used.

  4. Number of Participants With Change in Cytokine Levels With p Values <0.05

    Time frame: Baseline to up to 30 days post-treatment

    The changes in the cytokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.

  5. Number of Participants With Change in Chemokine Levels With p Values <0.05

    Time frame: Baseline to up to 30 days post-treatment

    The changes in the chemokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.

  6. Number of Participants With Change in Biomarker Levels With p Values <0.05

    Time frame: Baseline to up to 30 days post-treatment

    The changes in the cytokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.

  7. Incidence of Adverse Events as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

    Time frame: Up to 30 days

    Toxicity data will be summarized by frequency tables.

Sponsors and collaborators

Lead sponsor

National Cancer Institute (NCI)

Nih

Registry information

Official study title

Phase II Study of MK-2206 in Patients With Relapsed Lymphoma

Important dates

Study start
2010
Primary completion
2014
Study completion
2015
First posted
Dec 13, 2010
Registry last updated
Nov 4, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.