Adult Nasal Type Extranodal NK/T-cell LymphomaPhase 2NCT01258998
Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma
A Phase 2 study testing Akt inhibitor MK2206 and laboratory biomarker analysis in people with Adult Nasal Type Extranodal NK/T-cell Lymphoma and Anaplastic Large Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma
- What is being tested?
- Akt inhibitor MK2206 and laboratory biomarker analysis
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to Aug 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the objective response rate (ORR) of MK-2206 (Akt inhibitor MK2206) in patients with relapsed/refractory lymphoma.
SECONDARY OBJECTIVES:
- 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.
- 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, Cutaneous B-cell Non-Hodgkin Lymphoma
- Being tested
- Akt inhibitor MK2206, laboratory biomarker analysis
- Medical subject headings
- Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Leukemia, Lymphocytic, Chronic, B-Cell, Intraocular Lymphoma, Lymphoma, B-Cell, Marginal Zone, Lymphoma, T-Cell, Peripheral, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Akt inhibitor MK2206Drug
Also called MK2206
Given PO
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (Akt inhibitor MK2206) | Experimental | 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. Receives: Drug: Akt inhibitor MK2206; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Secondary outcomes (7)
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.
Measured: From treatment start date until the date of first documented progression or date of death from any cause, whichever came first.
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.
Measured: 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
Number of surviving participants without disease progression or death for any reason at one year post treatment. Kaplan-Meier method was used.
Measured: 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
The changes in the cytokine levels from baseline analyzed by Wilcoxon signed rank test. P values < 0.05 were considered statistically significant.
Measured: Baseline to up to 30 days post-treatment
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.
Measured: Baseline to up to 30 days post-treatment
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.
Measured: 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
Toxicity data will be summarized by frequency tables.
Measured: Up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2010 (estimated)
- Study startDec 2010
- Primary completionJul 2014
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult Nasal Type Extranodal NK/T-cell LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Yasuhiro Oki, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01258998
- Sponsor's protocol ID
- NCI-2012-02890
- Other IDs
- NCI-2012-02890, NCI-2011-00275, 2010-0261, 8728, N01CM00039, P30CA016672, N01CM62202
- Status last verified
- Oct 2020
- First submitted
- 10 Dec 2010
- Last updated
- 4 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 26213141
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of MK-2206 in Patients With Relapsed Lymphoma
- ClinicalTrials.gov ID
- NCT01258998
- Acronym / sponsor ID
- NCI-2012-02890
- 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, Cutaneous B-cell Non-Hodgkin Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2010
- Primary completion
- Jul 2014 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 13 Dec 2010 (estimated)
- Results
- Posted 10 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Determine the objective response rate (ORR) of MK-2206 (Akt inhibitor MK2206) in patients with relapsed/refractory lymphoma.
SECONDARY OBJECTIVES:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Akt inhibitor MK2206) | Experimental | Drug: Akt inhibitor MK2206, Other: laboratory biomarker analysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Akt inhibitor MK2206Also: MK2206Given PO | Drug | Treatment (Akt inhibitor MK2206) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (Akt inhibitor MK2206) |
Primary outcome
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.
7 secondary outcomes
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.
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.
Overall Survival
Time frame: 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
Number of Participants With Change in Chemokine Levels With p Values <0.05
Time frame: 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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26213141Oki 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yasuhiro Oki principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Akt inhibitor MK2206 and laboratory biomarker analysis in people with Adult Nasal Type Extranodal NK/T-cell Lymphoma and Anaplastic Large Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01258998, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2020.