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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

Phase 2
18 Years
Open (Enrolling)
Recurrent Adult Diffuse Large Cell Lymphoma

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Trial Information

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


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).


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

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

- 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

- 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

- 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

Type of Study:


Study Design:

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

Outcome Measure:

Overall response rate (complete response and partial response) in patients treated with selumetinib

Outcome Description:

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.

Outcome Time Frame:

Up to 3 years

Safety Issue:


Principal Investigator

Leo Gordon

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2010

Completion Date:

Related Keywords:

  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell



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