Imatinib Mesylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Who Have Received Chemotherapy

Imatinib Mesylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Who Have Received Chemotherapy
This study is ongoing, but not recruiting participants.

First Received on July 30, 2007.  
Last Updated on March 16, 2012  
History of Changes
Sponsor: Case Comprehensive Cancer Center
Collaborator: National Cancer Institute (NCI)
Information provided by (Responsible Party): Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00509093
  Purpose

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well imatinib mesylate works in treating patients with newly diagnosed acute myeloid leukemia who have received chemotherapy.

Condition Intervention Phase
Leukemia Drug: imatinib mesylate
Genetic: gene expression analysis
Genetic: mutation analysis
Genetic: polymerase chain reaction
Other: flow cytometry
Procedure: biopsy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Imatinib Mesylate (Gleevec) as Maintenance Therapy After Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed C-kit Positive Acute Myeloid Leukemia

Resource links provided by NLM:

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:

  • Progression-free survival [ Time Frame: 13 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

  • Toxicity as measured by NCI CTC v. 3.0 [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Correlation of c-kit expression with multidrug resistance gene expression (MDR1, MRP1, LRP, and BCRP) and AF1q expression [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 68
Study Start Date: December 2008
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Intervention Details:

    Drug: imatinib mesylate

    Patients will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. The study dose can be split but the dose of 600 mg must be given within a 12 hour period.
    Other Name: Gleevec

    Genetic: gene expression analysis

    Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed. Required samples include: 10 slides of cytospins from the initial newly diagnosed sample for immunohistochemistry. Additionally, paraffin blocks (3 thick sections and 2 thin sections) are needed. These assays will be performed by Dr. Francis Ali-Osman and Dr. Arati Rao at Duke University Medical Center.

    Samples will be sent to the following address:

    Dr. David Rizzieri 2400 Pratt Street Duke North Pavilion, Suite 100 Duke University Medical Center Durham, NC 27710 Phone number: (919) 668-1040

    Other Name: MRD

    Genetic: mutation analysis

    FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR.
    Other Name: FLT3

    Genetic: polymerase chain reaction

    4.4 AF1q gene analysis (on bone marrow aspirate): Diagnostic frozen samples will be analyzed in the lab of Dr. William Tse, if the participating site has these samples available from an existing tissue repository. Samples will be frozen in liquid nitrogen and shipped to Dr. Tse’s lab in dry ice. Once samples arrive at Dr. Tse’s lab, they will be stored in liquid nitrogen until analysis. Samples will be thawed and examined for viability using trypan blue staining. The pure blast population will be sorted out (500,000 to 1 million cells are needed). Total RNA will be isolated from marrow mononuclear cells using standard TriZol method and quantitative real-time PCR will be performed as according to (17).

    The address for Dr. Tse’s lab is:

    William Tse, M.D. 2nd Floor, PO Box 9162 Hematology/Oncology West Virginia University Mary Babb Randolph Cancer Center Morgantown, West Virginia 26506 Phone: 304-293-4980

    Other Name: AF1Q gene analysis

    Other: flow cytometry

    4.1 C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated as the c-kit mean channel number (MCN) of the blasts/ MCN auto fluorescence (See Examples, Figures 1 and 2 in Appendix 2). These calculations will be done centrally at the Cleveland Clinic by Dr. Eric Hsi in pathology. In cases where flow cytometry is done at the participating institution, these samples will be collected and analyzed per their local procedures. Flow cytometry and flow scatter gram results will be sent to Cleveland Clinic for review before the patient begins treatment.
    Other Name: C-kit MFI, CD117

    Procedure: biopsy

    Diagnostic bone marrow biopsy/aspirate must be done within 3 weeks of registration documenting complete remission
    Other Name: bone marrow biopsy/aspirate

Detailed Description:

OBJECTIVES:

Primary

  • To determine whether adding imatinib mesylate as maintenance therapy improves progression-free survival in patients with c-kit positive acute myeloid leukemia (AML) compared with historical controls.

Secondary

  • To assess the feasibility of administering imatinib mesylate as maintenance therapy after the completion of induction and consolidation therapy in these patients.
  • To evaluate potential mechanisms of relapse/resistance in c-kit positive AML by examining multidrug resistance gene expression and AF1q gene expression and to determine whether these levels correlate with c-kit expression.

OUTLINE: This is a multicenter study.

Patients receive oral imatinib mesylate once daily for up to 12 months.

Bone marrow and peripheral blood are collected at baseline. Laboratory endpoints are evaluated by flow cytometry; mutation and gene analysis by PCR.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

  • Age > 18.
  • Diagnostic bone marrow aspirate/ biopsy or peripheral blood confirming AML.
  • At the time of diagnosis, patients must have c-kit (also known as CD117) positive AML (20% or more of the blasts express c-kit[CD117]).
  • A flow scattergram (from the diagnostic AML specimen) must be available to calculate a c-kit MFI.
  • Patients must have received standard induction chemotherapy with ADE (cytarabine, daunorubicin, and etoposide) or with 7+3 (7 days of cytarabine continuous infusion and 3 days of an anthracycline (idarubicin, daunorubicin, or mitoxantrone). Patients with persistent leukemia on a Day 10-28 marrow may have received a second course of chemotherapy.
  • After the completion of induction therapy, patients must have attained a complete remission based on blood count recovery (neutrophil count > 1,000/µL, platelet count > 100,000/µL), and bone marrow aspirate and biopsy (< 5% myeloblasts).
  • For patients < 60 years of age, patients must have received at least 2 courses of post-remission therapy with at least intermediate dose (400 mg/m2/day). *Patients with t(8;21) or inversion 16 at the time of diagnosis must have received at least 2 courses of high dose cytarabine. For patients > or = 60 years of age, patients must have received 1 course of post-remission therapy (the type of chemotherapy will not be specified).
  • Patients must be registered on this study (maintenance Imatinib mesylate) within 60 days of the last dose of post-remission therapy.
  • A bone marrow aspirate and/or biopsy must be done within 3 weeks of registration documenting CR.
  • Women of childbearing potential and sexually active males must use an effective method of contraception.
  • Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
  • ECOG Performance Status 0-2.
  • Creatinine must be < 1.5 x upper limit of normal.
  • Total bilirubin must be < 2 mg/dl and AST and ALT must be < 2 times the upper limit of normal.
  • Previous treatment-related toxicities must have resolved to < Grade 1 excluding alopecia.
  • Written, voluntary informed consent.

EXCLUSION CRITERIA

  • Acute promyelocytic leukemia.
  • Patients with an autologous or allogeneic bone marrow transplant.
  • History of HIV.
  • Pregnant or breast-feeding.
  • Serious or poorly controlled medical conditions that would interfere with the protocol.
  • At the time of study entry, any medications which could significantly interact with imatinib mesylate (see Section 9.4) must be discontinued.
  • Patients with active extramedullary disease are not eligible.
  • Patient has received any other investigational agents within 28 days of first day of study drug dosing.
  • Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
  • Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
  • Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
  • Patient previously received radiotherapy to > or = 25 % of the bone marrow
  • Patient had a major surgery within 2 weeks prior to study entry.
  • Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00509093

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Anjali Advani, MD Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Principal Investigator: Brenda Cooper, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Additional Information:

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00509093    
History of Changes
Other Study ID Numbers: CASE4906, P30CA043703, CASE4906, AUS259, NCI-2010-01198
Study First Received: July 30, 2007
Last Updated: March 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:

adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myelomonocytic leukemia (M4)
adult acute megakaryoblastic leukemia (M7)
adult acute monoblastic leukemia (M5a)
adult acute monocytic leukemia (M5b)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute basophilic leukemia
adult acute eosinophilic leukemia
adult acute myeloid leukemia in remission

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2012

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