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

A Phase 2 Study of MK-2206 in Patients With Relapsed or Refractory Diffuse Large-B Cell Lymphoma

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01481129
Enrollment
22
Registered
2011-11-29
Start date
2011-12-31
Completion date
2014-06-30
Last updated
2017-09-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diffuse Large B Cell Lymphoma

Brief summary

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.

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.

Interventions

DRUGAkt Inhibitor MK2206

Given PO

OTHERLaboratory Biomarker Analysis

Correlative studies

OTHERPharmacological Study

Correlative studies

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Objective Response Rate According to the International Response Criteria for DLBCL (Cheson 2007)Up to 4 monthsRate of CR + PR according to Cheson 2007 after 4 months of treatment

Secondary

MeasureTime frameDescription
Duration of Responseup to 4 yearsDescribed in responding subjects using descriptive statistics (median, extreme values, etc.).
Overall SurvivalFrom the date of inclusion to the date of death from any cause, assessed up to 4 yearsAnalyzed 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.
Progression-free Survival (PFS)From the date of inclusion to the date of first documented disease progression, relapse or death from any cause, assessed up to 4 yearsAnalyzed 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.
Toxicity as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0Up to 30 days

Countries

France

Participant flow

Participants by arm

ArmCount
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. Akt Inhibitor MK2206: Given PO Laboratory Biomarker Analysis: Correlative studies Pharmacological Study: Correlative studies
22
Total22

Baseline characteristics

CharacteristicTreatment (Akt Inhibitor MK2206)
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
10 Participants
Age, Categorical
Between 18 and 65 years
12 Participants
Age, Continuous64.9 years
Region of Enrollment
France
22 participants
Sex: Female, Male
Female
10 Participants
Sex: Female, Male
Male
12 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
19 / 19
serious
Total, serious adverse events
8 / 19

Outcome results

Primary

Objective Response Rate According to the International Response Criteria for DLBCL (Cheson 2007)

Rate of CR + PR according to Cheson 2007 after 4 months of treatment

Time frame: Up to 4 months

ArmMeasureValue (NUMBER)
Treatment (Akt Inhibitor MK2206)Objective Response Rate According to the International Response Criteria for DLBCL (Cheson 2007)0 objective response
Secondary

Duration of Response

Described in responding subjects using descriptive statistics (median, extreme values, etc.).

Time frame: up to 4 years

Population: No responses were observed

Secondary

Overall Survival

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.

Time frame: From the date of inclusion to the date of death from any cause, assessed up to 4 years

ArmMeasureValue (MEDIAN)
Treatment (Akt Inhibitor MK2206)Overall Survival9.6 months
Secondary

Progression-free Survival (PFS)

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.

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

ArmMeasureValue (MEDIAN)
Treatment (Akt Inhibitor MK2206)Progression-free Survival (PFS)1.71 months
Secondary

Toxicity as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Time frame: Up to 30 days

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Treatment (Akt Inhibitor MK2206)Toxicity as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.019 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026