Selumetinib in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
This study is currently recruiting participants.
Verified April 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: April 10, 2013
Last verified: April 2013
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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: diagnostic 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 and partial response) 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 [complete response (CR), and partial response (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: The date of study entry to the date of death, assessed up to 3 years ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: The 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: From the time from study entry to any treatment failure, assessed up to 3 years ] [ Designated as safety issue: No ]
- Incidence of adverse events [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]The descriptions and grading scales found in the CTEP Version 4 of the NCI Common Terminology Criteria for Adverse Events (CTCAE) will be utilized for AE reporting.
| Estimated Enrollment: | 28 |
| Study Start Date: | December 2010 |
| Estimated Primary Completion Date: | February 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (selumetinib)
Patients receive selumetinib PO twice daily 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:
Other: diagnostic 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 pERK and several relevant target substrates (e.g., MCT-1, MNK, ELK, c-MYC, and HIF-1alpha) in peripheral blood studies.
OUTLINE: This is a multicenter study.
Patients receive selumetinib orally (PO) twice daily 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:
- Diagnosis of relapsed or refractory diffuse large B-cell lymphoma (transformed large cell lymphoma allowed)
- Must have received ≥ 1 and ≤ 6 prior therapeutic regimens
- No patients who are eligible for potentially curative treatment with bone marrow transplantation, unless patient refuses transplant option
- No active CNS involvement by lymphoma
- ECOG performance status of 0-2
- Life expectancy > 3 months
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 8.0 g/dL
- Serum bilirubin < 1.5 times upper limit of normal (ULN)
- AST or ALT < 2.5 times ULN
- Fertile patients must agree to use adequate contraception (hormonal, barrier method of birth control, or abstinence) prior to study entry, for the duration of study participation, and for 4 weeks (female) and 16 weeks (male) after completion of selumetinib
- Negative pregnancy test
- Not pregnant or nursing
- HIV-positive patients allowed provided CD4 count > 400 and have no AIDS-defining illnesses (other than non-Hodgkin lymphoma)
- No other active infection
No cardiac conditions, including any of the following:
- Uncontrolled hypertension (blood pressure ≥ 150/95 mm Hg despite optimal therapy)
- NYHA class II-IV heart failure
- Prior or concurrent cardiomyopathy
- Baseline LVEF ≤ 50%
- Atrial fibrillation with heart rate > 100 bpm
- Unstable ischemic heart disease (myocardial infarction within 6 months prior to starting treatment, or angina requiring > once weekly nitrates)
- 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)
- No history of a serious medical or psychiatric illness likely to interfere with participation in this clinical study
- No recent history of refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
- No concurrent vitamin E supplements or multivitamin supplements that provide a total daily dose in excess of 100% of the recommended daily allowance for vitamin E
- More than 21 days since prior chemotherapy, radiotherapy, immunotherapy, or systemic biologic anticancer therapy
- Prior autologous stem cell transplantation allowed, but no prior allogeneic stem cell transplant
- No prior MEK, Ras, or Raf inhibitors
- At least 1 month wash-out interval since another investigational product, systemic treatment, or radiotherapy
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent drugs that alter CYP450 3A4 (or cannot be changed to drugs that do not alter CYP450 3A4)
- No concurrent drugs that may significantly prolong the QTc
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01278615
Locations
| United States, Illinois | |
| Northwestern University | Recruiting |
| Chicago, Illinois, United States, 60611 | |
| Contact: Leo I. Gordon 312-695-4546 l-gordon@northwestern.edu | |
| Principal Investigator: Leo I. Gordon | |
| University of Chicago Comprehensive Cancer Center | Recruiting |
| Chicago, Illinois, United States, 60637-1470 | |
| Contact: Sonali M. Smith smsmith@medicine.bsd.uchicago.edu | |
| Principal Investigator: Walter M. Stadler | |
| Principal Investigator: Sonali M. Smith | |
| Decatur Memorial Hospital | Recruiting |
| Decatur, Illinois, United States, 62526 | |
| Contact: Krishna A. Rao krao@siumed.edu | |
| Principal Investigator: Krishna A. Rao | |
| Evanston CCOP-NorthShore University HealthSystem | Recruiting |
| Evanston, Illinois, United States, 60201 | |
| Contact: Bruce E. Brockstein bbrockstein@northshore.org | |
| Principal Investigator: Bruce E. Brockstein | |
| Ingalls Memorial Hospital | Recruiting |
| Harvey, Illinois, United States, 60426 | |
| Contact: Mark F. Kozloff mfkozloff@aol.com | |
| Principal Investigator: Sulochana D. Yalavarthi | |
| Principal Investigator: Mark F. Kozloff | |
| Illinois CancerCare-Peoria | Recruiting |
| Peoria, Illinois, United States, 61615 | |
| Contact: Timothy M. Kuzel cancer@northwestern.edu | |
| Principal Investigator: Sachdev P. Thomas | |
| Principal Investigator: Timothy M. Kuzel | |
| Southern Illinois University | Recruiting |
| Springfield, Illinois, United States, 62702 | |
| Contact: James L. Wade kcheek@dmhhs.org | |
| Principal Investigator: John E. Godwin | |
| Principal Investigator: James L. Wade | |
| United States, Indiana | |
| Fort Wayne Medical Oncology and Hematology Inc - State Boulevard | Recruiting |
| Fort Wayne, Indiana, United States, 46845 | |
| Contact: Sreenivasa R. Nattam ledgar@fwmoh.com | |
| Principal Investigator: Sreenivasa R. Nattam | |
| Indiana University Medical Center | Recruiting |
| Indianapolis, Indiana, United States, 46202 | |
| Contact: Noah M. Hahn nhahn@iupui.edu | |
| Principal Investigator: Noah M. Hahn | |
| United States, Maryland | |
| University of Maryland Greenebaum Cancer Center | Recruiting |
| Baltimore, Maryland, United States, 21201-1595 | |
| Contact: Martin J. Edelman medelman@umm.edu | |
| Principal Investigator: Aaron P. Rapoport | |
| Principal Investigator: Martin J. Edelman | |
| Saint Joseph Medical Center | Recruiting |
| Towson, Maryland, United States, 21204 | |
| Contact: Richard M. Schraeder patriciajohnson@catholichealth.net | |
| Principal Investigator: Richard M. Schraeder | |
| United States, Massachusetts | |
| University of Massachusetts Medical School | Recruiting |
| Worcester, Massachusetts, United States, 01655 | |
| Contact: Andrew J. Evans 212-523-7170 aevans@chpnet.org | |
| Principal Investigator: Andrew J. Evans | |
| United States, Michigan | |
| University of Michigan University Hospital | Recruiting |
| Ann Arbor, Michigan, United States, 48109 | |
| Contact: Maha H. Hussain 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 Bethany.Sleckman@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 jruan@med.cornell.edu | |
| Principal Investigator: Rebecca L. Elstrom | |
| Principal Investigator: Jia Ruan | |
Sponsors and Collaborators
Investigators
| Principal Investigator: | Leo Gordon | University of Chicago Comprehensive Cancer Center |
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, 12-0110, NU-10H03, CDR0000690641, N01CM00071 |
| Study First Received: | January 15, 2011 |
| Last Updated: | April 10, 2013 |
| 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 May 19, 2013