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Recurrent Adult Diffuse Large Cell LymphomaPhase 2NCT01278615

Selumetinib in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma

A Phase 2 study testing Laboratory Biomarker Analysis and Selumetinib in people with Recurrent Adult Diffuse Large Cell Lymphoma, run by National Cancer Institute (NCI) at 16 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II clinical trial is studying how well selumetinib works in treating patients with relapsed or refractory diffuse large B-cell lymphoma. Selumetinib 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
What is being tested?
Laboratory Biomarker Analysis and Selumetinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
16 sitesUnited States
Study dates
Dec 2010to May 2014
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

  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Relapsed or refractory diffuse large B-cell lymphoma (transformed large cell lymphomas are allowed to enroll)
  • Patients must have received at least one previous therapeutic regimen, and no more than 6 previous therapeutic regimens
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Life expectancy > 3 months
  • No chemotherapy, radiation therapy, immunotherapy, or experimental anticancer therapy within 28 days before beginning study treatment
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  • Human immunodeficiency virus (HIV)-positive patients are eligible if: the cluster of differentiation (CD)4 count is > 400, have no acquired immune deficiency syndrome (AIDS)-defining illnesses (other than non-Hodgkin lymphoma [NHL]), and they are not taking combination antiretroviral therapy (cART) at the time of study entry that would interfere with cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP4503A4)
  • No other active infection
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, or abstinence) prior to study entry, for the duration of study participation, and for 4 weeks after dosing with AZD6244 hyd-sulfate ceases; women of child-bearing potential must have a negative pregnancy test prior to entry; should a woman become pregnant or suspect she is pregnant while she or her partner participating in this study, the patient should inform her treating physician immediately; please note that the AZD6244 hyd-sulfate manufacturer recommends that adequate contraception for male patients should be used for 16 weeks post-last dose due to sperm life cycle
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with AZD6244 hyd-sulfate
  • Patients may have received prior autologous, but not prior allogeneic stem cell transplant; however, patients who are eligible for potentially curative treatment with bone marrow transplant should not be entered on this investigational trial, unless they refuse the transplant option (or are not eligible for transplantation)

Who cannot join

  • Any prior exposure to mitogen-activated protein kinase kinase (MEK), Ras, or v-raf murine sarcoma 3611 viral oncogene homolog (Raf) inhibitors
  • Patients with any active central nervous system (CNS) involvement by lymphoma are excluded
  • Patients that are taking drugs that alter CYP450 3A4 (or cannot be changed to drugs that do not alter CYP450 3A4) are excluded
  • Cardiac conditions as follows:
  • Uncontrolled hypertension (blood pressure [BP] >= 150/95 despite optimal therapy)
  • Heart failure New York Heart Association (NYHA) class II or above
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  • Prior or current cardiomyopathy
  • Baseline left ventricular ejection fraction (LVEF) =< 50%
  • Atrial fibrillation with heart rate > 100 beats per minute (bpm)
  • Unstable ischemic heart disease (myocardial infarction [MI] within 6 months prior to starting treatment, or angina requiring use of nitrates more than once weekly)
  • Patients are excluded if there is corrected QT (QTc) interval > 450 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome)
  • Patients are excluded if they are taking any drugs that may significantly prolong the QTc; these drugs are prohibited during the study; if the patient is taking one or more of these medications, they may enroll if all pertinent medications are stopped with the associated "wash out" periods
  • Absolute neutrophil count (ANC) < 1.5 x 10^9/L (1500 per mm^3)
  • Platelets < 100 x 10^9/L
  • Hemoglobin (Hgb) < 8.0 g/dL
  • Serum bilirubin >= 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) >= 2.5 x ULN (>= 5 ULN in presence of liver metastases)
  • There should be a minimum of a 1 month wash-out interval from another investigational product to AZD6244 hyd-sulfate dosing start plus recovery from side effects of investigational product
  • There should be a minimum of a 1 month wash-out interval from the end of previous systemic treatment and radiotherapy
  • Patients are excluded if there is a history of a serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Patients may not have recent history of refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

United States16 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • University of Maryland/Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Fort Wayne Medical Oncology and Hematology Inc-Parkview

    Fort Wayne, Indiana, 46845

  • Ingalls Memorial Hospital

    Harvey, Illinois, 60426

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Weill Medical College of Cornell University

    New York, New York, 10065

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Southern Illinois University

    Springfield, Illinois, 62702

  • Saint John's Mercy Medical Center

    St Louis, Missouri, 63141

  • University of Massachusetts Memorial Health Care

    Worcester, Massachusetts, 01605

Other trials in United States

About this study

Official title: A Single-Arm Phase II Clinical Trial With the Novel MEK Inhibitor AZD-6244 for the Treatment of MCT-1 Related Relapsed or Refractory Diffuse Large B-Cell Lymphoma

This phase II clinical trial is studying how well selumetinib works in treating patients with relapsed or refractory diffuse large B-cell lymphoma. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the overall response rate (combined complete remission [CR] and partial remission [PR]) of AZD6244 hyd-sulfate anti-MEK (selumetinib) therapy for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

SECONDARY OBJECTIVES:

  1. To evaluate the safety and tolerability of MEK inhibitor therapy. II. To determine the progression-free survival, time to treatment failure, duration of response, and overall survival with AZD6244 hyd-sulfate therapy.

III. To examine biomarkers through down-regulation of phosphorylated extracellular signal-related kinase (pERK) and several relevant target substrates (e.g., monocarboxylate transporter-1 [MCT-1], Menkes disease-associated protein [MNK], ELK, c-v-myc avian myelocytomatosis viral oncogene homolog [c-MYC], and hypoxia-inducible factor-1alpha [HIF-1a]) in peripheral blood studies.

OUTLINE: This is a multicenter study.

Patients receive selumetinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample and tumor tissue collection at baseline and at day 15 of course 1 for biomarker studies.

After completion of study therapy, patients are followed up every 3 months for up to 3 years.

Being tested
Laboratory Biomarker Analysis, Selumetinib
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • SelumetinibDrug

    Also called ARRY-142886, AZD6244, MEK Inhibitor AZD6244

    Given PO

Study groups in NCT01278615
Study groupRoleWhat they receive
Treatment (selumetinib)ExperimentalPatients receive selumetinib PO BID on days 1-28. Treatment repeats every 28 days for 8 courses in the absence of disease progression or unacceptable toxicity
Receives: Other: Laboratory Biomarker Analysis; Drug: Selumetinib

What is being measured

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

  1. Response Rate (Complete Response [CR] and Partial Response [PR]) in Patients Treated With Selumetinib

    Estimates of the response rate based on best response (CR and PR) with the exact two-sided 95% confidence intervals. Response for this lymphoma clinical study was measured utilizing "Non-Hodgkins Lymphoma Response Criteria". These criteria are based upon the criteria from the Revised Response Criteria for Malignant Lymphoma, (Cheson et al.), Journal of Clinical Oncology, 2007, Vol. 25:579-586.

    Measured: Up to 3 years

  2. Disease Control Rate (Complete Response [CR], Partial Response [PR], and Stable Disease [SD]) in Patients Treated With Selumetinib

    Estimates of the disease control rate with the exact two-sided 95% confidence intervals. Response was measured utilizing "Non-Hodgkins Lymphoma Response Criteria". These criteria are based upon the criteria from the Revised Response Criteria for Malignant Lymphoma, (Cheson et al.), Journal of Clinical Oncology, 2007, Vol. 25:579-586. Using these criteria, 'disease control rate' encompassed patients who had either a CR, PR, and SD.

    Measured: Up to 3 years

Secondary outcomes (5)

  1. Duration of Response

    The Kaplan-Meier procedure will be used to characterize the duration of response. Median time-to-event and the corresponding two-sided 95% confidence intervals will be provided.

    Measured: From the documented beginning of response (CR or PR) to the time of relapse, assessed up to 3 years

  2. Incidence of Adverse Events Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

    Percentage of patients experiencing any grade 3 or higher adverse event at least possibly attributed to the study drug. (Additional adverse event reporting will appear in the AE outcomes module.)

    Measured: Up to 3 years

  3. Overall Survival

    The Kaplan-Meier procedure will be used to characterize the survivorship function. Median time-to-death and the corresponding two-sided 95% confidence intervals will be provided.

    Measured: Date of study entry to the date of death, assessed up to 3 years

  4. Progression-free Survival

    The Kaplan-Meier procedure will be used to characterize the survivorship function. Median time-to-event and the corresponding two-sided 95% confidence intervals will be provided.

    Measured: Time from entry onto study until lymphoma progression or death from any cause, assessed up to 3 years

  5. Time to Treatment Failure

    The Kaplan-Meier procedure will be used to characterize the survivorship function. Median time-to-event and the corresponding two-sided 95% confidence intervals will be provided.

    Measured: Time from study entry to treatment failure, defined as lymphoma progression or withdrawal from treatment due to adverse events, assessed up to 3 years. Patients who die without progression while still on therapy will be censored as of the time of death.

Timeline

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

  1. First posted19 Jan 2011 (estimated)
  2. Study startDec 2010
  3. Primary completionFeb 2014
  4. Study completionMay 2014

Why it stopped: Closed Prematurely.

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01278615
Sponsor's protocol ID
NCI-2011-02558
Other IDs
NCI-2011-02558, NU-10H03, CDR0000690641, 12-0110, 8611, N01CM00071, N01CM62201, P30CA014599
Status last verified
Jul 2014
First submitted
15 Jan 2011
Last updated
3 Feb 2016
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis and Selumetinib in people with Recurrent Adult Diffuse Large Cell Lymphoma, run by National Cancer Institute (NCI) at 16 sites 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 11 inclusion and 21 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: stopped early, as of the sponsor's last update on 3 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites 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 3 Feb 2016). 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?

Response Rate (Complete Response [CR] and Partial Response [PR]) in Patients Treated With Selumetinib (time frame: Up to 3 years). The study lists 2 primary outcomes in all. 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 NCT01278615.

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 3 Feb 2016.

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