Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
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: azacitidine Drug: gemtuzumab ozogamicin |
Phase 2 |
| Study Type: | Interventional |
| 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: 30 days ] [ Designated as safety issue: No ]
- Survival rate [ Time Frame: 30 days after study registration ] [ 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.
- Cytogenic response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Estimated as the proportion of patients achieving major and minor responses.
| Estimated Enrollment: | 139 |
| Study Start Date: | December 2008 |
| Estimated Primary Completion Date: | June 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (azacitidine, gemtuzumab)
See Detailed Description
|
Drug: azacitidine
Given IV or SC
Other Names:
Drug: gemtuzumab ozogamicin
Given IV
Other Names:
|
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 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.
MAINTENANCE THERAPY: Patients receive azacitidine IV over 10-40 minutes or 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. 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.
Eligibility| Ages Eligible for Study: | 60 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Morphologically confirmed diagnosis of acute myeloidleukemia (AML)
- No acute promyelocytic leukemia (FAB M3)
- No blastic transformation of chronic myelogenous leukemia
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
- Must be registered on SWOG-S9910
- No CNS involvement
- Zubrod performance status 0-3
Total bilirubin ≤ 2.0 times upper limit of normal (ULN) (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 allowed
- AST or ALT ≤ 2.0 times ULN (unless the elevation is believed to be due to hepatic infiltration by AML)
- Serum creatinine ≤ 1.5 times ULN
- LVEF ≥ 40% by MUGA or ECHO AND no clinical evidence of congestive heart failure within the past 56 days
- No known hypersensitivity to azacitidine, mannitol, hydroxyurea, orgemtuzumab ozogamicin
- Negative pregnancy test
- Not pregnant or nursing
- Fertile patients must use effective contraception
HIV-positive patients must meet the following criteria:
- No history of AIDS-defining events
- CD4 cells ≥ 500/mm^3
- Viral load of < 50 copies HIV mRNA/mm^3 if on cART or < 25,000 copiesHIV mRNA if not on cART
- No zidovudine or stavudine as part of cART
- No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer or any diagnosis of malignancy made within the past 2 years 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
- Concurrent hormonal therapy allowed
- At least 6 months since prior chemotherapy or radiotherapy
No prior systemic chemotherapy for acute leukemiaexcept hydroxyurea
- Prior hydroxyurea to control high WBC count allowed
Contacts and Locations
Show 149 Study Locations| Principal Investigator: | Sucha Nand | Southwest Oncology Group |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00658814 History of Changes |
| Other Study ID Numbers: | NCI-2009-00790, S0703, U10CA032102 |
| Study First Received: | April 12, 2008 |
| Last Updated: | March 11, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Congenital Abnormalities Leukemia Leukemia, Erythroblastic, Acute Leukemia, Megakaryoblastic, Acute Leukemia, Monocytic, Acute Leukemia, Myeloid, Acute Leukemia, Myeloid Leukemia, Myelomonocytic, Acute Leukemia, Myelomonocytic, Chronic Neoplasms by Histologic Type Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases |
Myelodysplastic-Myeloproliferative Diseases Antibodies, Monoclonal Azacitidine Gemtuzumab Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Therapeutic Uses Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 22, 2013