Acute Myeloid Leukemia Clinical Trial
Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
Summary
This phase II trial is studying the side effects of giving azacitidine together with gemtuzumab ozogamicin to see how well it works in treating older patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Azacitidine may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as gemtuzumab ozogamicin, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving azacitidine together with gemtuzumab ozogamicin may kill more cancer cells.
Full Description
PRIMARY OBJECTIVES:
I. To test whether outcomes of patients of age 60 or older with previously untreated non-M3 acute myeloid leukemia treated with azacitidine plus gemtuzumab ozogamicin are sufficient to warrant phase III investigation.
II. To estimate the frequency and severity of toxicities of this regimen in the good- and poor-risk groups of patients.
III. To investigate in a preliminary manner the disease-free survival of patients who achieve complete remission and receive post-remission therapy on this study.
IV. To investigate in a preliminary manner the cytogenetic response rates of patients treated with this regimen.
V. To investigate in a preliminary manner the effects of cytogenetic abnormalities, promoter and global methylation changes, and multidrug resistance on overall survival and response to azacitidine plus gemtuzumab ozogamicin therapy.
OUTLINE: Patients are stratified according to risk status (good [60-69 years of age OR Zubrod performance status [PS] 0-1] vs poor [>= 70 years of age AND Zubrod PS 2-3]).
REMISSION INDUCTION THERAPY: Patients receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) once daily (QD) on days 1-7 and gemtuzumab ozogamicin IV over 2 hours on day 8. Patients with residual leukemia (blast count >= 5%) receive a second course of induction therapy beginning between days 15-29. Patients achieving complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi) go on to receive consolidation therapy.
CONSOLIDATION THERAPY: Patients receive one course of azacitidine and gemtuzumab ozogamicin as in induction therapy (with azacitidine given SC only).
MAINTENANCE THERAPY: Patients receive azacitidine SC on days 1-7. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsies for cytogenetic studies at baseline, remission, and relapse or progression (and at completion of treatment if it does not correspond to one of these time points). Marrow and blood samples are submitted to correlatives studies and submitted to Southwest Oncology Group (SWOG) acute lymphoblastic leukemia (ALL)/chronic lymphocytic leukemia (CLL)/chronic myelogenous leukemia (CML) Repository in Seattle, WA.
After completion of study therapy, patients are followed every 2 months for 2 years, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.
Eligibility Criteria
Inclusion Criteria:
Morphologically confirmed diagnosis of acute myeloid leukemia (AML) with classification other than WHO acute promyelocytic leukemia (FAB M3), based on bone marrow examination performed within 14 days prior to registration; patients with World Health Organization (WHO) acute promyelocytic leukemia (FAB M3) or blastic transformation of chronic myelogenous leukemia are not eligible
Zubrod performance status 0-3
No known hypersensitivity to azacitidine, mannitol, hydroxyurea, orgemtuzumab ozogamicin
No prior systemic chemotherapy for acute leukemia with the exception of hydroxyurea; administration of hydroxyurea to control high white blood cell (WBC) count prior to registration is permitted
Patients with a history of prior myelodysplastic syndrome (MDS) are eligible according to the following criteria:
No prior treatment of MDS with AML induction-type chemotherapy or high-dose chemotherapy with hematopoietic stem cell support
Prior cytarabine allowed if dose < 100 mg/m^2/day
Prior hematopoietic growth factors, thalidomide, lenalidomide, arsenic trioxide, and signal transduction inhibitors for treatment of MDS allowed
No prior treatment with azacitidine, decitabine, or gemtuzumab ozogamicin
At least 30 days since prior therapy for MDS and recovered
Bilirubin =< 2.0 x institutional upper limit of normal (IULN) within 14 days to registration, unless the elevation is believed to be due to hepatic infiltration by AML
Hyperbilirubinemia due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert syndrome or hemolysis is allowed
Serum glutamic oxaloacetic transaminase (SGOT) aspartate aminotransferase (AST) =< 2 x IULN, or serum glutamic pyruvate transaminase (SGPT) alanine aminotransferase (ALT) =< 2.0 x IULN , unless the elevation is believed to be due to hepatic infiltration by AML
Serum creatinine =< 1.5 x IULN
Left ventricle ejection fraction (LVEF) >= 40% by multi-gated acquisition scan (MUGA) or echocardiogram (ECHO) AND no clinical evidence of congestive heart failure within the past 56 days
Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 14 days prior to registration to S0703; specimens must be submitted to the site's preferred cytogenetics laboratory
Patients must consent to submit specimens to the Southwest Oncology Group (SWOG) acute lymphoblastic leukemia (ALL)/chronic lymphocytic leukemia (CLL)/chronic myelogenous leukemia (CML) repository for cellular and molecular studies; collection of pretreatment blood and/or marrow specimens must be completed within 14 days prior to registration; if a marrow specimen is available, either from the diagnostic marrow or a repeat pre-registration marrow, then it must be submitted along with a peripheral blood specimen; otherwise peripheral blood alone must be submitted; residual specimens will only be banked if the patient provides separate consent; sites are required to offer patients the opportunity to participate in banking
No central nervous system (CNS) involvement; if central nervous involvement is clinically suspected, it must be ruled out by a lumbar puncture
Women of reproductive potential must have a pregnancy test within 28 days prior to registration; patients must not be pregnant or nursing because of the teratogenic potential of the drugs used in this study; women/men of reproductive potential must have agreed to use an effective contraceptive method
Patients not known to be human immunodeficiency virus positive (HIV+) must be tested for HIV infection within 14 days prior to registration
HIV-positive patients must meet the following criteria:
No history of acquired immunodeficiency syndrome (AIDS)-defining events
CD4 cells >= 500/mm^3
Viral load of < 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on cART or < 25,000 copies HIV mRNA if not on cART
No zidovudine or stavudine as part of cART Patients who are HIV+ and do not meet all of these criteria will not be eligible for this study
No other prior malignancy except for a) adequately treated basal cell or squamous cell skin cancer or b) any diagnosis of malignancy made within the past 2 years earlier, of which there is no clinically evident cancer, and for which the patient has completed all chemotherapy and radiotherapy at least 6 months prior to study registration; prior treatment with AML induction-type chemotherapy is not allowed; concurrent hormonal therapy is allowed
All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
At the time of patient registration, the treating institution's name and identification (ID) number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
Patients must have complete remission (CR) or CRi, documented by blood and marrow examinations performed within 42 days before this registration
Following completion of induction therapy, the blood counts must recover to absolute neutrophil count (ANC) >= 1,000/mcL and platelets >= 90,000/mcL (without transfusion), and must be maintained at these levels during the 7 days prior to registration
Patients must have serum creatinine =< 1.5 x IULN and SGOT or SGPT =< 1.5 x IULN within 28 days before registration
Patients must have recovered to =< Grade 2 from any induction cycle non-hematologic toxicities
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There are 157 Locations for this study
Burbank California, 91505, United States
Palo Alto California, 94304, United States
Sacramento California, 95817, United States
Hartford Connecticut, 06105, United States
Boise Idaho, 83706, United States
Alton Illinois, 62002, United States
Decatur Illinois, 62526, United States
Decatur Illinois, 62526, United States
Elgin Illinois, 60123, United States
Maywood Illinois, 60153, United States
Mount Vernon Illinois, 62864, United States
Springfield Illinois, 62781, United States
Beech Grove Indiana, 46107, United States
Richmond Indiana, 47374, United States
Anthony Kansas, 67003, United States
Chanute Kansas, 66720, United States
Dodge City Kansas, 67801, United States
El Dorado Kansas, 67042, United States
Fort Scott Kansas, 66701, United States
Independence Kansas, 67301, United States
Kingman Kansas, 67068, United States
Lawrence Kansas, 66044, United States
Liberal Kansas, 67901, United States
Liberal Kansas, 67905, United States
Newton Kansas, 67114, United States
Overland Park Kansas, 66209, United States
Overland Park Kansas, 66213, United States
Parsons Kansas, 67357, United States
Prairie Village Kansas, 66208, United States
Pratt Kansas, 67124, United States
Salina Kansas, 67401, United States
Salina Kansas, 67401, United States
Shawnee Mission Kansas, 66204, United States
Topeka Kansas, 66606, United States
Wellington Kansas, 67152, United States
Wichita Kansas, 67208, United States
Wichita Kansas, 67208, United States
Wichita Kansas, 67214, United States
Wichita Kansas, 67214, United States
Wichita Kansas, 67214, United States
Wichita Kansas, 67214, United States
Winfield Kansas, 67156, United States
Lexington Kentucky, 40536, United States
Baton Rouge Louisiana, 70809, United States
New Orleans Louisiana, 70112, United States
Ann Arbor Michigan, 48106, United States
Ann Arbor Michigan, 48106, United States
Ann Arbor Michigan, 48109, United States
Battle Creek Michigan, 49017, United States
Big Rapids Michigan, 49307, United States
Dearborn Michigan, 48124, United States
Detroit Michigan, 48201, United States
Detroit Michigan, 48236, United States
Flint Michigan, 48503, United States
Flint Michigan, 48532, United States
Grand Rapids Michigan, 49503, United States
Grand Rapids Michigan, 49503, United States
Grand Rapids Michigan, 49503, United States
Jackson Michigan, 49201, United States
Lansing Michigan, 48912, United States
Livonia Michigan, 48154, United States
Muskegon Michigan, 49444, United States
Pontiac Michigan, 48341, United States
Port Huron Michigan, 48060, United States
Saginaw Michigan, 48601, United States
Southfield Michigan, 48075, United States
Traverse City Michigan, 49684, United States
Warren Michigan, 48093, United States
Wyoming Michigan, 49519, United States
Jackson Mississippi, 39216, United States
Cape Girardeau Missouri, 63701, United States
Cape Girardeau Missouri, 63703, United States
Kansas City Missouri, 64108, United States
Kansas City Missouri, 64111, United States
Kansas City Missouri, 64114, United States
Kansas City Missouri, 64116, United States
Kansas City Missouri, 64118, United States
Kansas City Missouri, 64132, United States
Lee's Summit Missouri, 64086, United States
Liberty Missouri, 64068, United States
Saint Joseph Missouri, 64506, United States
Saint Joseph Missouri, 64507, United States
Saint Louis Missouri, 63109, United States
Saint Louis Missouri, 63141, United States
Saint Louis Missouri, 63141, United States
Billings Montana, 59101, United States
Billings Montana, 59101, United States
Billings Montana, 59101, United States
Billings Montana, 59102, United States
Billings Montana, 59102, United States
Bozeman Montana, 59715, United States
Butte Montana, 59701, United States
Great Falls Montana, 59405, United States
Great Falls Montana, 59405, United States
Great Falls Montana, 59405, United States
Havre Montana, 59501, United States
Helena Montana, 59601, United States
Kalispell Montana, 59901, United States
Kalispell Montana, 59901, United States
Kalispell Montana, 59901, United States
Missoula Montana, 59802, United States
Missoula Montana, 59802, United States
Missoula Montana, 59804, United States
Missoula Montana, 59804, United States
Albuquerque New Mexico, 87102, United States
Rochester New York, 14642, United States
Charlotte North Carolina, 28204, United States
Goldsboro North Carolina, 27534, United States
Hendersonville North Carolina, 28791, United States
Rutherfordton North Carolina, 28139, United States
Winston-Salem North Carolina, 27104, United States
Akron Ohio, 44307, United States
Bellefontaine Ohio, 43311, United States
Chillicothe Ohio, 45601, United States
Cincinnati Ohio, 45219, United States
Columbus Ohio, 43214, United States
Columbus Ohio, 43215, United States
Columbus Ohio, 43215, United States
Columbus Ohio, 43222, United States
Columbus Ohio, 43228, United States
Dayton Ohio, 45405, United States
Dayton Ohio, 45406, United States
Dayton Ohio, 45409, United States
Dayton Ohio, 45415, United States
Dayton Ohio, 45459, United States
Delaware Ohio, 43015, United States
Findlay Ohio, 45840, United States
Franklin Ohio, 45005, United States
Greenville Ohio, 45331, United States
Kettering Ohio, 45429, United States
Lancaster Ohio, 43130, United States
Marietta Ohio, 45750, United States
Mount Vernon Ohio, 43050, United States
Newark Ohio, 43055, United States
Portsmouth Ohio, 45662, United States
Springfield Ohio, 45505, United States
Troy Ohio, 45373, United States
Westerville Ohio, 43081, United States
Wilmington Ohio, 45177, United States
Xenia Ohio, 45385, United States
Zanesville Ohio, 43701, United States
Clackamas Oregon, 97015, United States
Gresham Oregon, 97030, United States
Milwaukie Oregon, 97222, United States
Newberg Oregon, 97132, United States
Oregon City Oregon, 97045, United States
Portland Oregon, 97210, United States
Portland Oregon, 97213, United States
Portland Oregon, 97216, United States
Portland Oregon, 97225, United States
Portland Oregon, 97227, United States
Salem Oregon, 97301, United States
Tualatin Oregon, 97062, United States
Anderson South Carolina, 29621, United States
Charleston South Carolina, 29425, United States
Spartanburg South Carolina, 29303, United States
Amarillo Texas, 79106, United States
Anacortes Washington, 98221, United States
Bellingham Washington, 98225, United States
Bremerton Washington, 98310, United States
Burien Washington, 98166, United States
Issaquah Washington, 98029, United States
Kennewick Washington, 99336, United States
Mount Vernon Washington, 98274, United States
Poulsbo Washington, 98370, United States
Seattle Washington, 98104, United States
Seattle Washington, 98104, United States
Seattle Washington, 98109, United States
Seattle Washington, 98112, United States
Seattle Washington, 98122, United States
Seattle Washington, 98195, United States
Sedro-Woolley Washington, 98284, United States
Spokane Washington, 99202, United States
Spokane Washington, 99218, United States
Vancouver Washington, 98664, United States
Wenatchee Washington, 98801, United States
Casper Wyoming, 82609, United States
Sheridan Wyoming, 82801, United States
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