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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Myel

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 Summary:

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:
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

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


Original Primary Outcome:

  • Phase III trial justification
  • Toxicity
  • Disease-free survival
  • Cytogenic response rate
  • Effects of cytogenetic abnormalities, promoter and global methylation changes, and multidrug resistance on overall survival and response


Current Secondary Outcome:

  • 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.
  • 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.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: April 12, 2008
Date Started: December 2008
Date Completion:
Last Updated: May 8, 2017
Last Verified: November 2016