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Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma

Primary Purpose

Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Akt inhibitor MK2206
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Nasal Type Extranodal NK/T-cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (Akt inhibitor MK2206)

Arm Description

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.

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR)
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 Outcome Measures

Progression-free Survival
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.
Duration of Response
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.
Overall Survival
Number of surviving participants without disease progression or death for any reason at one year post treatment. Kaplan-Meier method was used.
Number of Participants With Change in Cytokine Levels With p Values <0.05
The changes in the cytokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.
Number of Participants With Change in Chemokine Levels With p Values <0.05
The changes in the chemokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.
Number of Participants With Change in Biomarker Levels With p Values <0.05
The changes in the cytokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.
Incidence of Adverse Events as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Toxicity data will be summarized by frequency tables.

Full Information

First Posted
December 10, 2010
Last Updated
October 14, 2020
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01258998
Brief Title
Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma
Official Title
Phase II Study of MK-2206 in Patients With Relapsed Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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, 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 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, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, T-cell Adult Acute Lymphoblastic Leukemia, T-cell Large Granular Lymphocyte Leukemia, Testicular Lymphoma, Waldenström Macroglobulinemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (Akt inhibitor MK2206)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Akt inhibitor MK2206
Other Intervention Name(s)
MK2206
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Progression-free Survival
Description
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.
Time Frame
From treatment start date until the date of first documented progression or date of death from any cause, whichever came first.
Title
Duration of Response
Description
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.
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.
Title
Overall Survival
Description
Number of surviving participants without disease progression or death for any reason at one year post treatment. Kaplan-Meier method was used.
Time Frame
From the start of treatment to death or 30 days after removal from the study whichever occurs first
Title
Number of Participants With Change in Cytokine Levels With p Values <0.05
Description
The changes in the cytokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.
Time Frame
Baseline to up to 30 days post-treatment
Title
Number of Participants With Change in Chemokine Levels With p Values <0.05
Description
The changes in the chemokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.
Time Frame
Baseline to up to 30 days post-treatment
Title
Number of Participants With Change in Biomarker Levels With p Values <0.05
Description
The changes in the cytokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.
Time Frame
Baseline to up to 30 days post-treatment
Title
Incidence of Adverse Events as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Description
Toxicity data will be summarized by frequency tables.
Time Frame
Up to 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yasuhiro Oki
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26213141
Citation
Oki Y, Fanale M, Romaguera J, Fayad L, Fowler N, Copeland A, Samaniego F, Kwak LW, Neelapu S, Wang M, Feng L, Younes A. Phase II study of an AKT inhibitor MK2206 in patients with relapsed or refractory lymphoma. Br J Haematol. 2015 Nov;171(4):463-70. doi: 10.1111/bjh.13603. Epub 2015 Jul 27.
Results Reference
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Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma

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