S0535, Gemtuzumab and Combination Chemotherapy in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia
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|ClinicalTrials.gov Identifier: NCT00551460|
Recruitment Status : Completed
First Posted : October 31, 2007
Results First Posted : December 22, 2017
Last Update Posted : December 22, 2017
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 find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Gemtuzumab may also stop the growth of promyelocytic leukemia by blocking blood flow to the cancer. Giving gemtuzumab together with combination chemotherapy may be more effective in treating promyelocytic leukemia.
PURPOSE: This phase II trial is studying how well giving gemtuzumab together with combination chemotherapy works in treating patients with previously untreated promyelocytic leukemia.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia||Drug: arsenic trioxide Drug: gemtuzumab ozogamicin Drug: mercaptopurine Drug: methotrexate Drug: tretinoin||Phase 2|
- To assess the event-free survival and death during the first six weeks in patients with previously untreated, high-risk acute promyelocytic leukemia treated with a combined regimen of tretinoin, arsenic trioxide, and gemtuzumab ozogamicin.
- To estimate the frequency and severity of toxicities of this regimen in this group of patients.
- To investigate the molecular response rate utilizing this regimen in high-risk patients.
- Induction chemotherapy: Patients receive oral tretinoin twice daily beginning on day 1 until CR (up to 90 days), gemtuzumab ozogamicin IV over 2 hours on day 1, and arsenic trioxide IV over 2 hours 5 days a week beginning on day 10 until CR (up to 60 days) in the absence of disease progression or unacceptable toxicity. Patients achieving A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to consolidation therapy after maintaining B1 peripheral blood status for ≥ 7 days.
Consolidation therapy: Beginning between 2-8 weeks after documentation of complete response (CR), patients receive consolidation therapy.
- Consolidation courses 1 and 2: Patients receive arsenic trioxide IV over 2 hours 5 days a week for 5 weeks. Treatment repeats every 7 weeks for up to 2 courses. Patients remaining in A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status continue with consolidation courses 3 and 4.
- Consolidation courses 3 and 4: Within 4 weeks of completing consolidation course 2, patients receive oral tretinoin twice daily on days 1-7 and daunomycin IV bolus or over 1 hour on days 1-3. Within 2-8 weeks after recovery to B1 peripheral blood status, patients receive consolidation course 4 as in course 3. Patients who remain in B1 peripheral blood and C1 extramedullary disease status continue on consolidation courses 5 and 6.
- Consolidation courses 5 and 6: Beginning between 2-8 weeks after recovery to B1 peripheral blood status, patients receive gemtuzumab IV over 2 hours on day 1. Between 2-8 weeks after recovery to B1 peripheral blood status, patients receive consolidation course 6 as in course 5. Patients who remain in A1 bone marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to maintenance therapy.
- Maintenance therapy: Beginning 2-8 weeks after recovery of blood counts, patients receive oral tretinoin twice daily on days 1-7 every other week for 1 year, oral mercaptopurine once daily for 1 year, and oral methotrexate once weekly for 1 year.
Patients undergo bone marrow aspirates and biopsies periodically during study. Samples are analyzed for cytogenetics by fluorescence in situ hybridization (FISH) and for PML-RARα by polymerase chain reaction (PCR).
After completion of study treatment, patients are evaluated at 3, 6, 9, 12, 18, 24, and 36 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||78 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||S0535, A Phase II Study of ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin in Patients With Previously Untreated High-Risk Acute Promyelocytic Leukemia|
|Study Start Date :||November 2007|
|Actual Primary Completion Date :||June 2017|
|Actual Study Completion Date :||June 2017|
ATRA 45mg/m2 PO D1-CR Gemtuzumab Ozogamicin 9 mg/m2 IV D1 Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk D10-CR
Consolidation 1 and 2:
Arsenic Trioxide 0.15 mg/kg/d IV 5days/wk x 5 weeks, repeat after 2 weeks rest
Consolidation 2 and 3:
ATRA 45 mg/m2 PO D1-7 Daunomycin 50 mg/m2/d IV D1-3
Consolidation 5 and 6:
GO 9mg/m2 IV D1
ATRA 45 mg/m2/d PO D1-7 every 14 days 6-MP 60 mg/m2/d PO daily for 1 year Methotrexate 20 mg/m2 PO once/wk for 1 year
Drug: arsenic trioxide
Drug: gemtuzumab ozogamicin
- Continuous Complete Remission at 3 Years [ Time Frame: 3 years ]Binary variable: yes if the patient achieves complete remission and remains in continuous complete remission until at least 3 years after entering the study; otherwise no.
- Mortality Rate at 6 Weeks [ Time Frame: 6 weeks ]
- Frequency of Toxicities [ Time Frame: Up to 3 years ]Adverse events that were possibly, probably or definitely related to study drug are reported.
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): NCT00551460
Show 192 Study Locations
|Study Chair:||Jeffrey E. Lancet, MD||H. Lee Moffitt Cancer Center and Research Institute|
|Study Chair:||Rami Komrokji, MD||H. Lee Moffitt Cancer Center and Research Institute|
|Study Chair:||Cheryl L. Willman, MD||University of New Mexico Cancer Center|
|Study Chair:||Marilyn L. Slovak, PhD||City of Hope Comprehensive Cancer Center|