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

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Brief Title

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

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

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.
    

Detailed 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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Complete Response

Secondary Outcome

 Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug

Condition

Acute Myeloid Leukemia

Intervention

Azacitidine

Study Arms / Comparison Groups

 Treatment (azacitidine, gemtuzumab)
Description:  See Detailed Description

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

133

Start Date

December 1, 2008


Primary Completion Date

June 1, 2013

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
      

Gender

All

Ages

60 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Sucha Nand, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00658814

Organization ID

NCI-2009-00790

Secondary IDs

NCI-2009-00790

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Sucha Nand, Principal Investigator, Southwest Oncology Group


Verification Date

March 2020