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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01278615
First received: January 15, 2011
Last updated: July 11, 2014
Last verified: July 2014

January 15, 2011
July 11, 2014
December 2010
May 2014   (final data collection date for primary outcome measure)
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.
Overall response rate (complete response and partial response) in patients treated with selumetinib [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01278615 on ClinicalTrials.gov Archive Site
  • 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 ]
    .
  • Adverse events of selumetinib [ Designated as safety issue: Yes ]
  • Progression-free survival, time to treatment failure, duration of response, and overall survival of patients treated with selumetinib [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Selumetinib in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Recurrent Adult Diffuse Large Cell Lymphoma
  • Drug: selumetinib
    Given PO
    Other Names:
    • ARRY-142886
    • AZD6244
  • Other: laboratory biomarker analysis
    Correlative studies
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
Interventions:
  • Drug: selumetinib
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
13
Not Provided
May 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01278615
NCI-2011-02558, NCI-2011-02558, NU-10H03, CDR0000690641, 12-0110, 8611, N01CM62201, P30CA014599, N01CM00071
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Leo Gordon University of Chicago
National Cancer Institute (NCI)
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP