Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

NCT00588809 | Completed Phase 2 Results

• 4 other identifiers: NCI-2009-0025015455BN01CM62209N01CM62201
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II clinical trial is studying how well selumetinib works in treating patients with recurrent or refractory acute myeloid leukemia. Selumetinib may stop the growth of cancer by blocking some of the enzymes needed for cell growth

Conditions

Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Response Rate for Subjects Without FLT3 ITD Mutation

  Responses were defined using standard criteria developed by an International Working Group. \[Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003;21:4642-9.\] In this primary outcome, we report the proportion of subjects without FLT3 ITD mutation that experienced a complete response (CR), partial response (PR), minor response (MR), or unconfirmed minor response (uMR).

  Up to 52 weeks

Secondary Outcomes (5)

• Proportion of Subjects With Baseline p-ERK Activation

  baseline (0 weeks)

• Proportion of Subjects With NRAS Mutation

  baseline (0 weeks)

• Proportion of Subjects With KRAS Mutation

  baseline (0 weeks)

• Proportion of Subjects With FLT3 ITD Mutation

  baseline (0 weeks)

• Proportion of Subjects With KIT Mutation

  baseline (0 weeks)

Study Arms (1)

Treatment (selumetinib)

EXPERIMENTAL

Patients receive selumetinib PO BID on days 1 -28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: selumetinib

Interventions

selumetinib DRUG

Given PO

Also known as: ARRY-142886, 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:

• Histologically or cytologically confirmed diagnosis of 1 of the following:
• Relapsed or refractory acute myeloid leukemia (AML)
• Secondary AML including AML arising from antecedent hematologic diseases (e.g., myelodysplastic syndrome, myeloproliferative disorders, or therapy-related AML)
• Elderly patients ≥ 60 years of age, previously untreated, and who are not candidates for or have refused standard chemotherapy are eligible for this trial
• Patients with relapsed acute promyelocytic leukemia (APL) who are FLT3+ and have failed both tretinoin and arsenic therapy are eligible for this trial
• No known active CNS disease
• ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
• Total bilirubin ≤ 2 mg/dL (unless due to disease, hemolysis, or Gilbert disease)
• In patients with associated hemolysis or Gilbert disease, a bilirubin of \> 2 mg/dL is allowed as a result of predominantly unconjugated hyperbilirubinemia
• AST/ALT \< 3 times upper limit of normal
• Creatinine \< 2 mg/dL
• Baseline pulse oximetry \> 92%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to, during, and for 4 weeks (16 week for males) after completion of study treatment

You may not qualify if:

• History of allergic reactions attributed to compounds of similar chemical or biological composition to AZD6244 or its excipient Captisol®
• QTc interval \> 450 msecs or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, or family history of long QT interval syndrome), including New York Heart Association class III or IV heart failure
• Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g., inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness or social situations that would limit compliance with study requirements

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637-1470, United States

Location

Related Publications (2)

• Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Lowenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD; International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-9. doi: 10.1200/JCO.2003.04.036.

  PMID: 14673054 BACKGROUND

• Jain N, Curran E, Iyengar NM, Diaz-Flores E, Kunnavakkam R, Popplewell L, Kirschbaum MH, Karrison T, Erba HP, Green M, Poire X, Koval G, Shannon K, Reddy PL, Joseph L, Atallah EL, Dy P, Thomas SP, Smith SE, Doyle LA, Stadler WM, Larson RA, Stock W, Odenike O. Phase II study of the oral MEK inhibitor selumetinib in advanced acute myelogenous leukemia: a University of Chicago phase II consortium trial. Clin Cancer Res. 2014 Jan 15;20(2):490-8. doi: 10.1158/1078-0432.CCR-13-1311. Epub 2013 Oct 31.

  PMID: 24178622 RESULT

MeSH Terms

Conditions

Leukemia, Promyelocytic, Acute; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid, Acute

Interventions

AZD 6244

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Results Point of Contact

• Title: Olatoyosi Odenike, MD
• Organization: The University of Chicago Medicine

todenike@medicine.bsd.uchicago.edu

(773) 702-6149

Study Officials

• Olatoyosi Odenike

  University of Chicago Comprehensive Cancer Center

  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: December 21, 2007
• First Posted: January 9, 2008
• Study Start: December 1, 2007
• Primary Completion: April 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 5, 2015
• Results First Posted: August 5, 2015

Record last verified: 2013-02

Locations

US (1)