Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
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.
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Secondary Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Drug: gemtuzumab ozogamicin
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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.|
- Probability of achieving CR or CRp [ Time Frame: 60 days ] [ Designated as safety issue: No ]
- Survival rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Disease-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Estimated by the method of Kaplan-Meier.
- Cytogenetic response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Estimated as the proportion of patients achieving major and minor responses.
|Study Start Date:||December 2008|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (azacitidine, gemtuzumab)
See Detailed Description
Given IV or SC during induction; given SC during consolidation and maintenance
Other Names:Drug: gemtuzumab ozogamicin
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 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 aza given SC only).
MAINTENANCE THERAPY: Patients receive azacitidine subcutaneously 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 SWOG ALL/CLL/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.