Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase II Trial of Azacitidine (NSC-102816) Plus Gemtuzumab Ozogamicin (NSC-720568) as Induction and Post-Remission Therapy in Patients of Age 60 and Older With Previously Untreated Non-M3 Acute Myeloid Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00658814
• Other study ID #: NCI-2009-00790
• Secondary ID: NCI-2009-00790SW
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 1, 2008
• Est. completion date: March 7, 2025

Study information

• Verified date: January 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 133
• Est. completion date: March 7, 2025
• Est. primary completion date: June 1, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Adult Acute Megakaryoblastic Leukemia
• Adult Acute Monoblastic Leukemia
• Adult Acute Monocytic Leukemia
• Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11
• Adult Acute Myeloid Leukemia With Maturation
• Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11
• Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1
• Adult Acute Myeloid Leukemia Without Maturation
• Adult Acute Myelomonocytic Leukemia
• Adult Erythroleukemia
• Adult Pure Erythroid Leukemia
• Leukemia
• Leukemia, Erythroblastic, Acute
• Leukemia, Megakaryoblastic, Acute
• Leukemia, Monocytic, Acute
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Acute
• Secondary Acute Myeloid Leukemia

Intervention

Drug:
• Azacitidine
Given IV or SC during induction; given SC during consolidation and maintenance
• Gemtuzumab Ozogamicin
Given IV

Locations

Country	Name	City	State
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Saint Anthony's Health	Alton	Illinois
United States	The Don and Sybil Harrington Cancer Center	Amarillo	Texas
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	AnMed Health Hospital	Anderson	South Carolina
United States	Michigan Cancer Research Consortium NCORP	Ann Arbor	Michigan
United States	Trinity Health Saint Joseph Mercy Hospital Ann Arbor	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Hospital District Sixth of Harper County	Anthony	Kansas
United States	Hematology/Oncology Clinic PLLC	Baton Rouge	Louisiana
United States	Bronson Battle Creek	Battle Creek	Michigan
United States	Franciscan Saint Francis Health-Beech Grove	Beech Grove	Indiana
United States	Mary Rutan Hospital	Bellefontaine	Ohio
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Saint Vincent Frontier Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Missouri Hospital	Cape Girardeau	Missouri
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	University of Cincinnati Cancer Center-UC Medical Center	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Columbus NCI Community Oncology Research Program	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	Dayton NCI Community Oncology Research Program	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Beaumont Hospital - Dearborn	Dearborn	Michigan
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Advocate Sherman Hospital	Elgin	Illinois
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan
United States	Corewell Health Grand Rapids Hospitals - Butterworth Hospital	Grand Rapids	Michigan
United States	Trinity Health Grand Rapids Hospital	Grand Rapids	Michigan
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Wayne Hospital	Greenville	Ohio
United States	Legacy Mount Hood Medical Center	Gresham	Oregon
United States	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut
United States	Northern Montana Hospital	Havre	Montana
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Allegiance Health	Jackson	Michigan
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Glacier Oncology PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Heartland Hematology and Oncology Associates Incorporated	Kansas City	Missouri
United States	North Kansas City Hospital	Kansas City	Missouri
United States	Research Medical Center	Kansas City	Missouri
United States	Saint Joseph Health Center	Kansas City	Missouri
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University Health Truman Medical Center	Kansas City	Missouri
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Kettering Medical Center	Kettering	Ohio
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	Fairfield Medical Center	Lancaster	Ohio
United States	University of Michigan Health - Sparrow Lansing	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Saint Luke's East - Lee's Summit	Lee's Summit	Missouri
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Southwest Medical Center	Liberal	Kansas
United States	Liberty Radiation Oncology Center	Liberty	Missouri
United States	Trinity Health Saint Mary Mercy Livonia Hospital	Livonia	Michigan
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	Loyola University Medical Center	Maywood	Illinois
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Specialists	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Skagit Valley Hospital	Mount Vernon	Washington
United States	Trinity Health Muskegon Hospital	Muskegon	Michigan
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Licking Memorial Hospital	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Menorah Medical Center	Overland Park	Kansas
United States	Saint Luke's South Hospital	Overland Park	Kansas
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Trinity Health Saint Joseph Mercy Oakland Hospital	Pontiac	Michigan
United States	Lake Huron Medical Center	Port Huron	Michigan
United States	Adventist Medical Center	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Legacy Good Samaritan Hospital and Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Kansas City NCI Community Oncology Research Program	Prairie Village	Kansas
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Reid Health	Richmond	Indiana
United States	University of Rochester	Rochester	New York
United States	Rutherford Hospital	Rutherfordton	North Carolina
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Ascension Saint Mary's Hospital	Saginaw	Michigan
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Saint Joseph Oncology Inc	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri
United States	Salem Hospital	Salem	Oregon
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salina Regional Health Center	Salina	Kansas
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Advent Health - Shawnee Mission Medical Center	Shawnee Mission	Kansas
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Ascension Providence Hospitals - Southfield	Southfield	Michigan
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	Memorial Medical Center	Springfield	Illinois
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Cotton O'Neil Cancer Center / Stormont Vail Health	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	Saint Ann's Hospital	Westerville	Ohio
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Clinton Memorial Hospital/Foster J Boyd Regional Cancer Center	Wilmington	Ohio
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Southeast Clinical Oncology Research Consortium NCORP	Winston-Salem	North Carolina
United States	University of Michigan Health - West	Wyoming	Michigan
United States	Greene Memorial Hospital	Xenia	Ohio
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response	Morphologic complete remission (CR): ANC >=1,000/mcL, platelet count >=100,000/mcL, <5% bone marrow blasts, no Auer rods, no evidence of extramedullary disease. Morphologic complete remission with incomplete blood count recovery (CRi): Same as CR but ANC may be <1,000/mcL and/or platelet count <100,000/mcL.	Up to 60 days
Primary	30-Day Survival	Patients surviving more than 30 days after study registration	30 days
Secondary	Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug	Only adverse events that are possibly, probably or definitely related to study drug are reported.	Up to 5 years
Secondary	Relapse-free Survival	Relapse-free survival (RFS) is defined for all patients who achieve CR or CRi. RFS is measured from the date CR or CRi is first achieved until relapse or death form any cause, with observation censored on the date of last contact for patients last known to be alive without report of relapse. Relapse from CR/CRi is defined as reappearance of leukemic blasts in the peripheral blood; or > 5% blasts in the bone marrow not attributable to another cause; or appearance or reappearance of extramedullary disease.	Up to 5 years