Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma

October 14, 2020 updated by: National Cancer Institute (NCI)

Phase II Study of MK-2206 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Other: laboratory biomarker analysis
Correlative studies
Drug: Akt inhibitor MK2206
Given PO
Other Names:
  • MK2206

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
4 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From treatment start date until the date of first documented progression or date of death from any cause, whichever came first.
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.
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.
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.
From the start of treatment to death or 30 days after removal from the study whichever occurs first
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.
Baseline to up to 30 days post-treatment
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.
Baseline to up to 30 days post-treatment
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.
Baseline to up to 30 days post-treatment
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.
Up to 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Yasuhiro Oki, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2010

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

December 10, 2010

First Submitted That Met QC Criteria

December 10, 2010

First Posted (Estimate)

December 13, 2010

Study Record Updates

Last Update Posted (Actual)

November 4, 2020

Last Update Submitted That Met QC Criteria

October 14, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02890 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • P30CA016672 (U.S. NIH Grant/Contract)
  • N01CM62202 (U.S. NIH Grant/Contract)
  • N01CM00039 (U.S. NIH Grant/Contract)
  • NCI-2011-00275
  • 2010-0261 (Other Identifier: M D Anderson Cancer Center)
  • 8728 (CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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