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

This study is currently recruiting participants.
Verified August 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01278615
First received: January 15, 2011
Last updated: March 28, 2014
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Recurrent Adult Diffuse Large Cell Lymphoma
Drug: selumetinib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall response rate (complete response [CR] and partial response [PR]) in patients treated with selumetinib [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Estimates of the response rate based on best response (CR and PR) and the tumor control rate (CR, PR, and stable disease [SD]) will be provided together with the exact two-sided 95% confidence intervals.


Secondary Outcome Measures:
  • Duration of response [ Time Frame: From the documented beginning of response (CR or PR) to the time of relapse, assessed up to 3 years ] [ Designated as safety issue: No ]
    The Kaplan-Meier procedure will be used to characterize the survivorship function. Median time-to-events and the corresponding two-sided 95% confidence intervals will be provided for each of these variables.

  • Overall survival [ Time Frame: Date of study entry to the date of death, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Time from entry onto study until lymphoma progression or death from any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    The Kaplan-Meier procedure will be used to characterize the survivorship function. Median time-to-events and the corresponding two-sided 95% confidence intervals will be provided for each of these variables.

  • Time to treatment failure [ Time Frame: Time from study entry to any treatment failure, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    .


Estimated Enrollment: 28
Study Start Date: December 2010
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (selumetinib)
Patients 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
Drug: selumetinib
Given PO
Other Names:
  • ARRY-142886
  • AZD6244
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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)

Exclusion Criteria:

  • 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
    • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01278615

Locations
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Sonali M. Smith    773-834-2895    smsmith@medicine.bsd.uchicago.edu   
Principal Investigator: Sonali M. Smith         
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Leo I. Gordon    312-695-4546    l-gordon@northwestern.edu   
Principal Investigator: Leo I. Gordon         
Decatur Memorial Hospital Recruiting
Decatur, Illinois, United States, 62526
Contact: James L. Wade    217-876-6600    JLWADE3@sbcglobal.net   
Principal Investigator: James L. Wade         
NorthShore University HealthSystem-Evanston Hospital Recruiting
Evanston, Illinois, United States, 60201
Contact: Bruce E. Brockstein    847-570-2515    bbrockstein@northshore.org   
Principal Investigator: Bruce E. Brockstein         
Ingalls Memorial Hospital Recruiting
Harvey, Illinois, United States, 60426
Contact: Mark F. Kozloff    708-339-4800    mfkozloff@aol.com   
Principal Investigator: Mark F. Kozloff         
Illinois CancerCare-Peoria Recruiting
Peoria, Illinois, United States, 61615
Contact: Sachdev P. Thomas    309-243-3605    sthomas@illinoiscancercare.com   
Principal Investigator: Sachdev P. Thomas         
Southern Illinois University Recruiting
Springfield, Illinois, United States, 62702
Contact: Krishna A. Rao    217-545-7969    jgodwin@siumed.edu   
Principal Investigator: Krishna A. Rao         
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc-Parkview Recruiting
Fort Wayne, Indiana, United States, 46845
Contact: Sreenivasa R. Nattam    260-484-8830    ledgar@fwmoh.com   
Principal Investigator: Sreenivasa R. Nattam         
Indiana University Medical Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Stephanie A. Wagner    317-962-9000    wagnerst@iupui.edu   
Principal Investigator: Stephanie A. Wagner         
United States, Maryland
University of Maryland Greenebaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201-1595
Contact: Amy S. Kimball    410-328-6373    akimball@umm.edu   
Principal Investigator: Amy S. Kimball         
United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Andrew M. Evens    617-636-8077    AEvens@tuftsmedicalcenter.org   
Principal Investigator: Andrew M. Evens         
University of Massachusetts Memorial Health Care Recruiting
Worcester, Massachusetts, United States, 01605
Contact: Jan Cerny    774-443-3903    Jan.Cerny@umassmemorial.org   
Principal Investigator: Jan Cerny         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Maha H. Hussain    734-936-8906    mahahuss@umich.edu   
Principal Investigator: Maha H. Hussain         
United States, Missouri
Saint John's Mercy Medical Center Recruiting
Saint Louis, Missouri, United States, 63141
Contact: Bethany G. Sleckman    314-251-7057    slecbg@stlo.mercy.net   
Principal Investigator: Bethany G. Sleckman         
United States, New York
Weill Medical College of Cornell University Recruiting
New York, New York, United States, 10065
Contact: Jia Ruan    646-962-2064    jruan@med.cornell.edu   
Principal Investigator: Jia Ruan         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jason R. Westin    713-792-3750    jwestin@mdanderson.org   
Principal Investigator: Jason R. Westin         
Sponsors and Collaborators
Investigators
Principal Investigator: Leo Gordon University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01278615     History of Changes
Other Study ID Numbers: NCI-2011-02558, NCI-2011-02558, NU-10H03, CDR0000690641, 12-0110, 8611, N01CM00071, P30CA014599, N01CM62201
Study First Received: January 15, 2011
Last Updated: March 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on April 16, 2014