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

NCT ID: NCT01278615

Last Updated: 2016-02-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2014-05-31

Brief 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.

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.

Conditions

Recurrent Adult Diffuse Large Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Selumetinib

Intervention Type: DRUG

Given PO

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Selumetinib

Given PO

Intervention Type: DRUG

Other Intervention Names

ARRY-142886; AZD6244; MEK Inhibitor AZD6244

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Leo Gordon

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Decatur Memorial Hospital

Decatur, Illinois, United States

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Southern Illinois University

Springfield, Illinois, United States

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, United States

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

University of Massachusetts Memorial Health Care

Worcester, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Saint John's Mercy Medical Center

St Louis, Missouri, United States

Weill Medical College of Cornell University

New York, New York, United States

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

NCI-2011-02558

Identifier Type: REGISTRY

Identifier Source: secondary_id

NU-10H03

Identifier Type: -

Identifier Source: secondary_id

CDR0000690641

Identifier Type: -

Identifier Source: secondary_id

12-0110

Identifier Type: OTHER

Identifier Source: secondary_id

8611

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62201

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014599

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02558

Identifier Type: -

Identifier Source: org_study_id