Combination Chemotherapy With or Without Gemtuzumab in Treating Young Patients With Newly Diagnosed Acute Myeloid Leukemia
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Purpose
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab, 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 combination chemotherapy together with gemtuzumab may kill more cancer cells. It is not yet known whether combination chemotherapy is more effective with or without gemtuzumab in treating patients with newly diagnosed acute myeloid leukemia.
PURPOSE: This randomized phase III trial is studying combination chemotherapy and gemtuzumab to see how well they work compared with combination chemotherapy alone in treating young patients with newly diagnosed acute myeloid leukemia.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia |
Drug: asparaginase Drug: cytarabine Drug: daunorubicin hydrochloride Drug: etoposide Drug: gemtuzumab ozogamicin Drug: mitoxantrone hydrochloride |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Primary Purpose: Treatment |
| Official Title: | A Phase III Randomized Trial of Gemtuzumab Ozogamicin (Mylotarg) Combined With Conventional Chemotherapy for De Novo Acute Myeloid Leukemia (AML) in Children, Adolescents, and Young Adults |
- Event-free survival [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Remission induction rate after 2 courses of induction therapy [ Designated as safety issue: No ]
- Disease-free survival [ Designated as safety issue: No ]
- Mortality during first 3 courses of therapy [ Designated as safety issue: No ]
- Time to marrow recovery [ Designated as safety issue: No ]
- Toxicities, including infectious complications [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 1000 |
| Study Start Date: | August 2006 |
| Estimated Primary Completion Date: | August 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Arm I (standard therapy)
Patients receive intrathecal (IT) cytarabine (ARA-C) at diagnosis or on day 1 of treatment or twice a week for up to 6 doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin on days 1, 3, and 5; and a 4-hour infusion of etoposide on days 1-5. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hour infusion of daunorubicin on days 1, 3, and 5; and a 4-hour infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hour infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hour infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. After 3 weeks of rest, they receive a 3-hour infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. |
Drug: asparaginase
Given intramuscularly
Drug: cytarabine
Given IV
Drug: daunorubicin hydrochloride
Given IV over 6 hours
Drug: etoposide
Given IV over 1-4 hours
Drug: mitoxantrone hydrochloride
Given IV over 1 hour
|
|
Experimental: Arm II
Patients receive IT ARA-C at diagnosis or on day 1 of treatment or twice a week for up to six doses. They also receive an infusion of ARA-C on days 1-10; a 6-hour infusion of daunorubicin on days 1, 3, and 5; a 4-hour infusion of etoposide on days 1-5; and a 2-hour infusion of gemtuzumab on day 6. After 3 weeks of rest, patients receive IT ARA-C on day 1. They also receive an infusion of ARA-C on days 1-8; a 6-hour infusion of daunorubicin on days 1, 3, and 5; and a 4-hour infusion of etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1 and 1-hour infusions of ARA-C and etoposide on days 1-5. After 3 weeks of rest, some patients receive IT ARA-C on day 1; a 2-hour infusion of ARA-C on days 1-4; and a 1-hour infusion of mitoxantrone on days 3-6. They also receive a 2-hour infusion of gemtuzumab on day 7. After 3 weeks of rest, they receive a 3-hour infusion of ARA-C on days 1, 2, 8, and 9 and an injection of asparaginase on days 2 and 9. |
Drug: asparaginase
Given intramuscularly
Drug: cytarabine
Given IV
Drug: daunorubicin hydrochloride
Given IV over 6 hours
Drug: etoposide
Given IV over 1-4 hours
Drug: gemtuzumab ozogamicin
Given IV over 2 hours
Drug: mitoxantrone hydrochloride
Given IV over 1 hour
|
Show Detailed Description Eligibility| Ages Eligible for Study: | up to 29 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Newly diagnosed acute myeloid leukemia (AML)
Meets customary criteria for AML with ≥ 20% bone marrow blasts (by WHO classification)
Patients with < 20% bone marrow blasts and cytopenia or myelodysplastic syndromes (e.g., chronic myelomonocytic leukemia, refractory anemia [RA], RA with excess blasts, RA with ringed sideroblasts) are eligible provided 1 of the following criteria is met:
- Karyotypic abnormality characteristic of de novo AML (t[8;21][q22;q22], inv[16][p13q22], t[16;16][p13;q22], or 11q23 abnormalities)
- Unequivocal presence of megakaryoblasts (by WHO classification)
- Isolated myeloid sarcoma (i.e., myeloblastoma or chloroma) allowed regardless of bone marrow results
- Infants < 1 month of age with progressive disease* are eligible NOTE: *Infants < 1 month of age with AML may be given supportive care until it is clear that the leukemia is not regressing (i.e., the disappearance of peripheral blasts and the normalization of peripheral blood counts)
- Patients with Down syndrome ≥ 4 years of age are eligible
- No juvenile myelomonocytic leukemia
- No Fanconi's anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome
- No promyelocytic leukemia (M3)
- No secondary or treatment-related AML
Matched family donor criteria (for patients with intermediate-risk or high-risk disease):
- HLA-A, -B, -C, and -DRB1, identical or 1 antigen or allele mismatched by molecular high resolution technique
- All available first-degree family members (parents and siblings) must be HLA typed
- No syngeneic donors
Matched alternative donor criteria (for patients with high-risk disease):
- HLA-A, -B, -C, and -DRB1, identical or 1 antigen or allele mismatched donor
- HLA-A, -B, and -DRB1 4 of 6 antigen matched unrelated cord blood donor
- Mismatched family member donor with ≥ 1 haplotype match or 5 of 6 antigen phenotypic match
PATIENT CHARACTERISTICS:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
No prior chemotherapy, radiation therapy, or any antileukemic therapy
- Topical or inhalation steroids for other conditions allowed
- Intrathecal cytarabine given at diagnosis allowed
- No other prior treatment for AML
- No concurrent peripheral blood stem cell transplantation in patients with matched family donor
Contacts and Locations
Show 198 Study Locations| Study Chair: | Alan S. Gamis, MD, MPH | Children's Mercy Hospital |
| Investigator: | Richard Aplenc, MD, MSCE | Children's Hospital of Philadelphia |
More Information
Additional Information:
Publications:
| Responsible Party: | Gregory H. Reaman, Children's Oncology Group - Group Chair Office |
| ClinicalTrials.gov Identifier: | NCT00372593 History of Changes |
| Other Study ID Numbers: | CDR0000487497, COG-AAML0531 |
| Study First Received: | September 6, 2006 |
| Last Updated: | July 19, 2012 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Cancer Institute (NCI):
|
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) untreated adult acute myeloid leukemia untreated childhood acute myeloid leukemia and other myeloid malignancies adult acute basophilic leukemia adult acute eosinophilic leukemia adult acute minimally differentiated myeloid leukemia (M0) adult acute myeloblastic leukemia without maturation (M1) adult acute myeloblastic leukemia with maturation (M2) adult acute myelomonocytic leukemia (M4) adult acute monoblastic leukemia (M5a) adult acute monocytic leukemia (M5b) |
adult erythroleukemia (M6a) adult pure erythroid leukemia (M6b) adult acute megakaryoblastic leukemia (M7) childhood acute basophilic leukemia childhood acute eosinophilic leukemia childhood acute minimally differentiated myeloid leukemia (M0) childhood acute myeloblastic leukemia without maturation (M1) childhood acute myeloblastic leukemia with maturation (M2) childhood acute myelomonocytic leukemia (M4) childhood acute monocytic leukemia (M5b) childhood acute monoblastic leukemia (M5a) childhood acute erythroleukemia (M6) childhood acute megakaryocytic leukemia (M7) |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Neoplasms by Histologic Type Neoplasms Etoposide phosphate Gemtuzumab Asparaginase Cytarabine Daunorubicin Etoposide Mitoxantrone Antineoplastic Agents Therapeutic Uses Pharmacologic Actions |
Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antibiotics, Antineoplastic Antineoplastic Agents, Phytogenic Analgesics Sensory System Agents Peripheral Nervous System Agents Central Nervous System Agents |
ClinicalTrials.gov processed this record on May 22, 2013