Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With AML Leukemia
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00049517 |
|
Recruitment Status :
Completed
First Posted : January 27, 2003
Results First Posted : February 12, 2013
Last Update Posted : June 15, 2023
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
RATIONALE: Giving combination chemotherapy before a stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the transplanted stem cells. When the healthy stem cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. If the patient's stem cells are to be transplanted, the patient is also treated with a monoclonal antibody, such as gemtuzumab ozogamicin, to kill any remaining cancer cells or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without gemtuzumab ozogamicin followed by stem cell transplant in treating acute myeloid leukemia.
PURPOSE: This randomized phase III trial is studying combination chemotherapy, gemtuzumab ozogamicin, and stem cell transplant to see how well they work compared to combination chemotherapy and peripheral stem cell transplant alone in treating patients with acute myeloid leukemia.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Leukemia | Biological: sargramostim Drug: busulfan Drug: cyclophosphamide Drug: cytarabine Drug: gemtuzumab ozogamicin (GO) Drug: Daunorubicin Procedure: Autologous HCT Procedure: Allogeneic HCT | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 657 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III Trial in Adult Acute Myeloid Leukemia: Daunorubicin Dose-Intensification Prior to Risk-Allocated Autologous Stem Cell Transplantation |
| Actual Study Start Date : | December 19, 2002 |
| Actual Primary Completion Date : | March 2009 |
| Actual Study Completion Date : | December 2019 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Standard Daunorubicin Then Autologous HCT
Induction: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course. Consolidation/Transplant: Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts. The patients undergoing autologous hematopoietic cell transplantation (HCT) received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses (without pharmacokinetic sampling) followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days. |
Biological: sargramostim
Given IV or as an injection
Other Name: Leukine Drug: busulfan Given IV
Other Name: Myleran Drug: cyclophosphamide Given IV
Other Names:
Drug: cytarabine Given as a continuous infusion
Other Name: cytosine arabinoside Drug: Daunorubicin Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
Procedure: Autologous HCT Autologous hematopoietic cell transplantation
Other Name: Autologous hematopoietic cell transplantation |
|
Experimental: High-dose Daunorubicin Then Autologous HCT
Induction: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course. Consolidation/Transplant: Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts. The patients undergoing autologous hematopoietic cell transplantation (HCT) received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses (without pharmacokinetic sampling) followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days. |
Biological: sargramostim
Given IV or as an injection
Other Name: Leukine Drug: busulfan Given IV
Other Name: Myleran Drug: cyclophosphamide Given IV
Other Names:
Drug: cytarabine Given as a continuous infusion
Other Name: cytosine arabinoside Drug: Daunorubicin Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
Procedure: Autologous HCT Autologous hematopoietic cell transplantation
Other Name: Autologous hematopoietic cell transplantation |
|
Experimental: Standard Daunorubicin Then GO/Autologous HCT
Induction: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course. Consolidation/Transplant: Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts. patients randomized to the investigational arm received a single dose of Gemtuzumab ozogamicin (GO) at 6 mg/m2 followed by sargramostim 250 μ/m2 until recovery of counts. The patients undergoing autologous HCT received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days. |
Biological: sargramostim
Given IV or as an injection
Other Name: Leukine Drug: busulfan Given IV
Other Name: Myleran Drug: cyclophosphamide Given IV
Other Names:
Drug: cytarabine Given as a continuous infusion
Other Name: cytosine arabinoside Drug: gemtuzumab ozogamicin (GO) Given IV
Other Name: Mylotarg Drug: Daunorubicin Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
Procedure: Autologous HCT Autologous hematopoietic cell transplantation
Other Name: Autologous hematopoietic cell transplantation |
|
Experimental: High-dose Daunorubicin Then GO/Autologous HCT
Induction: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course. Consolidation/Transplant: Before initiating consolidation therapy, patients with CR were randomized to a standard or an investigational arm. All patients received 2 cycles of high-dose cytarabine therapy (3 g/m2 given IV over a 3-hour period every 12 hours every other day for a total of 6 doses), followed by sargramostim 250 μg/m2 until recovery of blood counts. patients randomized to the investigational arm received a single dose of Gemtuzumab ozogamicin (GO) at 6 mg/m2 followed by sargramostim 250 μ/m2 until recovery of counts. The patients undergoing autologous HCT received intravenous busulfan 0.8 mg/kg every 6 hours for 16 doses followed by intravenous cyclophosphamide 60 mg/kg daily for 2 days. |
Biological: sargramostim
Given IV or as an injection
Other Name: Leukine Drug: busulfan Given IV
Other Name: Myleran Drug: cyclophosphamide Given IV
Other Names:
Drug: cytarabine Given as a continuous infusion
Other Name: cytosine arabinoside Drug: gemtuzumab ozogamicin (GO) Given IV
Other Name: Mylotarg Drug: Daunorubicin Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
Procedure: Autologous HCT Autologous hematopoietic cell transplantation
Other Name: Autologous hematopoietic cell transplantation |
|
Active Comparator: Standard Daunorubicin Then Allogeneic HCT or no Consolidation
Induction: Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course. Consolidation/Transplant: Patients without CR did not receive any consolidation treatment. Patients in CR with an unfavorable cytogenetic profile or an initial white blood cell count > 100,000/μL were to proceed to allogeneic HCT if they had a suitable human leukocyte antigen (HLA)-matched sibling donor available. |
Drug: cytarabine
Given as a continuous infusion
Other Name: cytosine arabinoside Drug: Daunorubicin Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
Procedure: Allogeneic HCT Allogeneic hematopoietic cell transplantation
Other Name: Allogeneic hematopoietic cell transplantation |
|
Experimental: High-dose Daunorubicin Then Allogeneic HCT or no Consolidation
Induction: Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course. Consolidation/Transplant: Patients without CR did not receive any consolidation treatment. Patients in CR with an unfavorable cytogenetic profile or an initial white blood cell count > 100,000/μL were to proceed to allogeneic HCT if they had a suitable human leukocyte antigen (HLA)-matched sibling donor available. |
Drug: cytarabine
Given as a continuous infusion
Other Name: cytosine arabinoside Drug: Daunorubicin Given intravenously daily for 3 days at a dose of either 45 or 90 mg/m2.
Other Names:
Procedure: Allogeneic HCT Allogeneic hematopoietic cell transplantation
Other Name: Allogeneic hematopoietic cell transplantation |
- Overall Survival (Induction Phase) [ Time Frame: Assessed during the first 4 months, then at least every three months for 2 years. then every six months until 5 years after study entry and every 12 months thereafter. ]Overall survival is defined as the time from randomization in the induction phase to death.
- Disease-free Survival (Consolidation Phase) [ Time Frame: Assessed during the first 4 months, then at least every three months for 2 years. then every six months until five years after study entry, and every 12 months thereafter. ]Disease-free survival is defined from the time of the confirmation of a complete remission via biopsy to the relapse of the disease.
- Overall Survival (Consolidation Phase) [ Time Frame: Assessed during the first 4 months, then at least every three months for 2 years. then every six months until five years after study entry, and every 12 months thereafter. ]Overall survival is defined as the time from randomization in the consolidation phase to death.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 16 Years to 60 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
-
Morphologically confirmed acute myeloid leukemia (AML) (greater than 20% blasts in the peripheral blood or marrow) meeting any of the following criteria:
-
Recurrent cytogenetic translocations
- t(8;21)(q22;q22)
-
Bone marrow eosinophil abnormalities
- inv(16)(p13;q22)
- t(16;16)(p13;q22)
- 11q23 abnormalities
- Multilineage dysplasia without presence of myelodysplastic syndromes (MDS)
- Minimally differentiated AML
- AML without maturation
- AML with maturation
- AML not otherwise categorized
- Acute myelomonocytic leukemia
- Acute monocytic leukemia
- Acute erythroid leukemia
- Acute megakaryocytic leukemia
- Acute basophilic leukemia
-
- Patients undergoing allogeneic transplantation must have a sibling donor match defined as human leukocyte antigen (HLA) match or haplotype match with one locus mismatch on other haplotype
- Age 16 to 60
- Eastern Cooperative Oncology Group (ECOG) performance status 0-4
- Aspartate aminotransferase (AST) less than 4 times upper limit of normal (ULN)
- Alkaline phosphatase less than 4 times ULN
- Creatinine no greater than 2.0 mg/dL
- Creatinine clearance at least 50 mL/min
- Left ventricular ejection fraction (LVEF) at least 45% by post-induction multigated acquisition (MUGA) scan
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- Prior hydroxyurea allowed
- Prior corticosteroids allowed
Exclusion Criteria:
-
Recurrent cytogenetic translocations
- Acute promyelocytic leukemia (PML) with t(15;17)(q22;q21)
- Variant acute PML with t(v;17)
- Multilineage dysplasia with prior MDS
-
Acute panmyelosis with myelofibrosis
- Blastic transformation of chronic myelogenous leukemia
- Secondary AML (chemotherapy-induced or evolved from MDS)
- Pregnant or nursing
- Bilirubin greater than 2.0 mg/dL (unless related to Gilbert's syndrome or hemolysis)
- Significant cardiac disease requiring active therapy (e.g., digoxin, diuretics, antiarrhythmics, or antianginal medications)
- Prior biologic therapy
- Prior cytotoxic chemotherapy for any malignancy
- Prior radiotherapy for any malignancy
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00049517
Show 99 study locations
| Study Chair: | Hugo F. Fernandez, MD | H. Lee Moffitt Cancer Center and Research Institute |
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Eastern Cooperative Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00049517 |
| Other Study ID Numbers: |
CDR0000258113 U10CA021115 ( U.S. NIH Grant/Contract ) E1900 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) ) |
| First Posted: | January 27, 2003 Key Record Dates |
| Results First Posted: | February 12, 2013 |
| Last Update Posted: | June 15, 2023 |
| Last Verified: | June 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
|
acute myeloid leukemia autologous transplantation gemtuzumab ozogamicin |
|
Leukemia Neoplasms by Histologic Type Neoplasms Hematologic Diseases Cytarabine Cyclophosphamide Busulfan Daunorubicin Gemtuzumab Sargramostim Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating |
Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Antineoplastic Agents, Immunological Immunotoxins Immunoconjugates |