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Accelerated Phase Chronic Myelogenous LeukemiaPhase 1NCT01231919

MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia

A Phase 1 study testing Akt inhibitor MK2206, diagnostic laboratory biomarker analysis and pharmacological study in people with Accelerated Phase Chronic Myelogenous Leukemia and Acute Leukemias of Ambiguous Lineage, run by National Cancer Institute (NCI) at 25 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial is studying the side effects, best way to give, and best dose of Akt inhibitor MK2206 (MK2206) in treating patients with recurrent or refractory solid tumors or leukemia. MK2206 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
Akt inhibitor MK2206, diagnostic laboratory biomarker analysis and pharmacological study
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
25 sitesin 2 countries
Study dates
Jan 2011to Apr 2013
Phase
Phase 1
Are there results?
None posted in the registry

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 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must have a body surface area > 0.5 m^2 when enrolling on dose levels 0 or 1 of the every other day schedule; no body surface area (BSA) restrictions apply to patients enrolling on higher dose levels; no BSA restrictions apply to patients enrolling on any dose level of the weekly schedule.
  • Diagnosis:
  • Part A (both schedules): Patients must have a diagnosis of recurrent or refractory solid tumors, including central nervous system (CNS) tumors or lymphoma; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
  • Part B (both schedules): Patients must have a diagnosis of recurrent or refractory leukemia
  • Disease status:
  • Solid tumors: Patients must have either measurable or evaluable disease
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  • Leukemia: Patients must have >= 5% blasts in the bone marrow; active extramedullary disease (except for leptomeningeal disease) may also be present
  • Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; note: neurologic deficits in patients with CNS tumors must have been relatively stable for a minimum of 1 week prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy
  • Myelosuppressive chemotherapy:
  • Solid tumors: Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
  • Leukemia:
  • Patients with leukemia who relapse while receiving standard maintenance chemotherapy will not be required to have a waiting period before enrollment onto this study
  • Patients who relapse while they are not receiving standard maintenance therapy, must have fully recovered from all acute toxic effects of prior therapy. At least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea
  • Note: Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of MK-2206
  • At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
  • At least 7 days after the last dose of a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
  • At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines
  • At least 3 half-lives of the antibody after the last dose of a monoclonal antibody
  • >= 2 weeks for local palliative radiation therapy (XRT) (small port); >= 24 weeks must have elapsed if prior total body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; >= 6 weeks must have elapsed if other substantial bone marrow (BM) radiation
  • Stem cell infusion without TBI: No evidence of active graft vs. host disease and >= 8 weeks must have elapsed since transplant or stem cell infusion
  • Bone marrow transplantation: >= 3 months prior to study enrollment
  • For patients with solid tumors without known bone marrow involvement including patients who are status post stem cell transplantation:
  • Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
  • Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
  • For patients with solid tumors with known bone marrow metastatic disease:
  • These patients are eligible for study provided they meet the blood count criteria and are not known to be refractory to red cell or platelet transfusions; note: these patients are not evaluable for hematologic toxicity
  • For patients with leukemia (Part B):
  • Blood counts are not required to be normal prior to enrollment on this trial; however, platelet count has to be >= 20,000/mm^3 (may receive platelet transfusions)
  • Creatinine clearance or radioisotope GFR >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
  • 1 to < 2 years: 0.6 mg/dL
  • 2 to < 6 years: 0.8 mg/dL
  • 6 to < 10 years: 1 mg/dL
  • 10 to < 13 years: 1.2 mg/dL
  • 13 to < 16 years: 1.5 (male), 1.4 (female)
  • >= 16 years: 1.7 (male), 1.4 (female)
  • Patients with solid tumors:
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin >= 2 g/dL
  • Patients with leukemias:
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
  • SGPT (ALT) =< 225 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin >= 2 g/dL
  • Corrected QT interval (QTc) =< 450 msec
  • Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and well controlled
  • Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] v4) resulting from prior therapy must be =< grade 2
  • All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
  • Slides or tissue blocks from either initial diagnosis or relapse must be available for central review; tissue blocks or slides must be sent; if tissue blocks or slides are unavailable, the study chair must be notified prior to study enrollment

Who cannot join

  • Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
  • Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days are not eligible
  • Patients who are currently receiving another investigational drug are not eligible
  • Patients who are currently receiving other anticancer agents are not eligible [except leukemia patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy]; patients with leukemia may receive intrathecal therapy
  • Patients must not be receiving enzyme-inducing anticonvulsants
  • Patients receiving insulin or growth hormone therapy are not eligible
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  • Patients on medications that may cause corrected QT (QTc) interval prolongation are not eligible
  • Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post transplant are not eligible for this trial
  • Patients must be able to swallow whole tablets; nasogastric or G tube administration is not allowed
  • Patients who have an uncontrolled infection are not eligible
  • Patients with known type I or type II diabetes mellitus are not eligible
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Trial locations and contacts

25 sites in 2 countries.

25 sites in 2 countries

United States23 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia, 30322

  • Mark O Hatfield-Warren Grant Magnuson Clinical Center

    Bethesda, Maryland, 20892

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60614

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University Medical Center

    Indianapolis, Indiana, 46202

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • University of Minnesota Medical Center-Fairview

    Minneapolis, Minnesota, 55455

  • Columbia University Medical Center

    New York, New York, 10032

  • Childrens Hospital of Orange County

    Orange, California, 92868-3874

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • University of California San Francisco Medical Center-Parnassus

    San Francisco, California, 94143

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

Canada2 sites

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: A Phase I Study of MK-2206, an AKT Inhibitor, in Pediatric Patients With Recurrent or Refractory Solid Tumors or Leukemia

This phase I trial is studying the side effects, best way to give, and best dose of Akt inhibitor MK2206 (MK2206) in treating patients with recurrent or refractory solid tumors or leukemia. MK2206 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the maximum-tolerated dose (MTD) and/or recommended phase 2 dose of MK-2206 (Akt inhibitor MK2206) administered orally every other day (schedule 1) or once weekly (schedule 2) to children with refractory or recurrent solid malignancies, including central nervous system (CNS) tumors or lymphomas.

II. To define and describe the toxicities of MK-2206 in children with refractory solid malignancies administered on this schedule.

III. To assess the tolerability of MK-2206 at the solid tumor MTD in patients with recurrent or refractory leukemia.

IV. To characterize the pharmacokinetics of MK-2206 in children with recurrent or refractory cancer. (exploratory)

SECONDARY OBJECTIVES:

  1. To preliminarily define the antitumor activity of MK-2206 within the confines of a phase 1 study.(exploratory) II. To evaluate biological activity of MK-2206 by measuring phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling in tumor and peripheral blood mononuclear cells and measure the expression of biomarkers related to AKT activation phenotypes. (exploratory)

OUTLINE: This is a dose-escalation study (part A) followed by treatment at the maximum-tolerated dose (part B).

Patients receive Akt inhibitor MK2206 orally (PO) every other day (schedule 1) OR once weekly (schedule 2) on days 1-28. Treatment repeats every 28 days for up 12 courses (1 year) in the absence of disease progression or unacceptable toxicity.

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

Being tested
Akt inhibitor MK2206, diagnostic laboratory biomarker analysis, pharmacological study
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Leukemia, Biphenotypic, Acute, Leukemia, Myeloid, Acute, Myeloproliferative Syndrome, Transient, Leukemia, Large Granular Lymphocytic, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Blast Crisis, Blastic Plasmacytoid Dendritic Cell Neoplasm

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

  • diagnostic laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT01231919
Study groupRoleWhat they receive
Treatment (Akt inhibitor)ExperimentalPatients receive oral Akt inhibitor MK2206 every other day (schedule 1) OR once weekly (schedule 2) on days 1-28. Treatment repeats every 28 days for up 12 courses (1 year) in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Akt inhibitor MK2206; Other: diagnostic laboratory biomarker analysis; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD and/or recommended phase 2 dose of Akt inhibitor MK2206 determined according to incidence of dose-limiting toxicities (DLTs) graded using CTCAE v4.0 (Part A)

    The MTD will be the maximum dose at which fewer than one-third of patients experience DLT during course 1 of therapy.

    Measured: 28 days

Secondary outcomes (4)

  1. Pharmacokinetic (PK) parameters of Akt inhibitor MK-2206

    Summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

    Measured: Baseline, 0.5, 1.5, 3, 6-8, 24, 48 hours day 1 course 1; pre-dose and 6-8 hours post-dose (optional) day 15 (Schedule 1); baseline, 0.5, 1.5, 3, 6-8, 24, 48 hours day 1 course 1; pre-dose days 8 and 15; 6-8 hours post-dose day 15 (optional) (Schedule 2)

  2. Antitumor activity assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.1

    Measured: Up to 30 days

  3. Levels of activation of downstream signaling molecules

    Summarized using descriptive statistics at each timepoint. The Wilcoxon signed-rank test or Friedman's test may be used as a preliminary test of change in activity over two or more timepoints.

    Measured: Up to day 15 of course 1

  4. Mutations or amplification of upstream signaling molecules

    Summarized using descriptive statistics at each timepoint. The Wilcoxon signed-rank test or Friedman's test may be used as a preliminary test of change in activity over two or more timepoints.

    Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Nov 2010 (estimated)
  2. Study startJan 2011
  3. Primary completionApr 2013

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01231919
Sponsor's protocol ID
NCI-2011-02612
Other IDs
NCI-2011-02612, CDR0000687929, COG-ADVL1013, ADVL1013, ADVL1013, U01CA097452
Status last verified
Apr 2013
First submitted
29 Oct 2010
Last updated
29 Apr 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Akt inhibitor MK2206, diagnostic laboratory biomarker analysis and pharmacological study in people with Accelerated Phase Chronic Myelogenous Leukemia and Acute Leukemias of Ambiguous Lineage, run by National Cancer Institute (NCI) at 25 sites in 2 countries.

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 50 inclusion and 12 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 29 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, Canada. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

MTD and/or recommended phase 2 dose of Akt inhibitor MK2206 determined according to incidence of dose-limiting toxicities (DLTs) graded using CTCAE v4.0 (Part A) (time frame: 28 days). 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 NCT01231919.

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 29 Apr 2014.

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