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

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ClinicalTrials.gov Identifier: NCT00658814
Recruitment Status : Active, not recruiting
First Posted : April 15, 2008
Results First Posted : January 6, 2014
Last Update Posted : October 18, 2022
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief 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.

Condition or disease Intervention/treatment Phase
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 With t(9;11)(p21.3;q23.3); MLLT3-MLL Adult Acute Myeloid Leukemia Without Maturation Adult Acute Myelomonocytic Leukemia Adult Erythroleukemia Adult Pure Erythroid Leukemia Secondary Acute Myeloid Leukemia Drug: Azacitidine Drug: Gemtuzumab Ozogamicin Phase 2

Detailed Description:


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 133 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 1, 2008
Actual Primary Completion Date : June 1, 2013

Arm Intervention/treatment
Experimental: Treatment (azacitidine, gemtuzumab)
See Detailed Description
Drug: Azacitidine
Given IV or SC during induction; given SC during consolidation and maintenance
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • Onureg
  • U-18496
  • Vidaza

Drug: Gemtuzumab Ozogamicin
Given IV
Other Names:
  • Calicheamicin-Conjugated Humanized Anti-CD33 Monoclonal Antibody
  • CDP-771
  • CMA-676
  • gemtuzumab
  • hP67.6-Calicheamicin
  • Mylotarg
  • WAY-CMA-676

Primary Outcome Measures :
  1. Complete Response [ Time Frame: Up to 60 days ]
    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.

  2. 30-Day Survival [ Time Frame: 30 days ]
    Patients surviving more than 30 days after study registration

Secondary Outcome Measures :
  1. Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [ Time Frame: Up to 5 years ]
    Only adverse events that are possibly, probably or definitely related to study drug are reported.

  2. Relapse-free Survival [ Time Frame: Up to 5 years ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00658814

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Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Sucha Nand Southwest Oncology Group
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00658814    
Other Study ID Numbers: NCI-2009-00790
NCI-2009-00790 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
S0703 ( Other Identifier: SWOG )
S0703 ( Other Identifier: CTEP )
U10CA032102 ( U.S. NIH Grant/Contract )
First Posted: April 15, 2008    Key Record Dates
Results First Posted: January 6, 2014
Last Update Posted: October 18, 2022
Last Verified: October 2022
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Monocytic, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Megakaryoblastic, Acute
Leukemia, Erythroblastic, Acute
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Antineoplastic Agents, Immunological
Antibiotics, Antineoplastic