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

NCT01278615 | Terminated Phase 2 Results DMC

• 8 other identifiers: NCI-2011-02558NU-10H03CDR000069064112-01108611N01CM00071N01CM62201P30CA014599
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 16

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.

Conditions

Recurrent Adult Diffuse Large Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 3 years

• 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.

  Up to 3 years

Secondary Outcomes (5)

• Duration of Response

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

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

  Up to 3 years

• Overall Survival

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

• Progression-free Survival

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

• Time to Treatment Failure

  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.

Study Arms (1)

Treatment (selumetinib)

EXPERIMENTAL

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

Other: Laboratory Biomarker Analysis; Drug: Selumetinib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (selumetinib)

Selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD6244, MEK Inhibitor AZD6244

Treatment (selumetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (16)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Southern Illinois University

Springfield, Illinois, 62702, United States

Location

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, 46845, United States

Location

Indiana University/Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Massachusetts Memorial Health Care

Worcester, Massachusetts, 01605, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Saint John's Mercy Medical Center

St Louis, Missouri, 63141, United States

Location

Weill Medical College of Cornell University

New York, New York, 10065, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Sonali M. Smith
• Organization: University of Chicago

smsmith@medicine.bsd.uchicago.edu

773-834-2895

Study Officials

• Leo Gordon

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2011
• First Posted: January 19, 2011
• Study Start: December 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: May 1, 2014
• Last Updated: February 3, 2016
• Results First Posted: February 3, 2016

Record last verified: 2014-07

Locations

US (16)