Trials / Completed

CompletedNCT00416598

Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia

Phase II Study of Maintenance Therapy With Decitabine (NSC #127716) Following Standard Induction and Cytogenetic Risk-Adapted Intensification in Previously Untreated Patients With AML < 60 Years

Status: Completed
Phase: Phase 2
Study type: Interventional
Enrollment: 546 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 15 Years – 59 Years
Healthy volunteers: Not accepted

Summary

This phase II trial is studying the side effects and how well decitabine works when given as maintenance therapy after standard therapy in treating patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, daunorubicin, etoposide, busulfan, and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving decitabine as maintenance therapy after standard therapy may keep cancer cells from coming back.

Detailed description

PRIMARY OBJECTIVES: I. To determine the efficacy, feasibility, and toxicities when one year of maintenance therapy with decitabine is given to patients \< 60 years with untreated acute myeloid leukemia (AML) who achieve and maintain first complete remission (CR) following an established induction and intensification regimen. II. To determine the 1-year disease free survival rate for AML patients in first CR treated with maintenance decitabine. SECONDARY OBJECTIVES: I. To measure biologic response to decitabine in evaluable patients with fusion genes to determine eradication of minimal residual disease. II. To measure surrogates for deoxyribonucleic acid (DNA) demethylation including downregulation of DNA methyltransferase 1 (DNMT1) and induction of fetal hemoglobin. III. To examine the significance of gene re expression following ex vivo decitabine exposure in primary AML cells taken at the time of diagnosis on clinical outcome and on gene expression at the time of relapse after in vivo decitabine exposure. IV. To continue to evaluate the effectiveness of a cytogenetically risk-adapted approach for consolidation therapy for patients with core binding factor (CBF) or non-CBF AML. V. To continue the investigation begun in Cancer and Leukemia Group B (CALGB) 19808 aimed at correlation of the rate of relapse and toxicity with intravenous (IV) busulfan pharmacokinetics when busulfan and etoposide are used as the preparative regimen for autologous stem cell transplantation for AML patients in first CR. VI. To correlate outcome measures such as complete response (CR), disease-free survival (DFS), event-free survival (EFS), and overall survival (OS), with pretreatment characteristics such as age, sex, race, blood counts, morphology, immunophenotype, cytogenetics, and molecular features of AML. OUTLINE: REMISSION INDUCTION THERAPY: Patients receive cytarabine IV over 168 hours on days 1-7 and daunorubicin hydrochloride IV over 5-10 minutes and etoposide IV over 2 hours on days 1-3. Patients undergo bone marrow biopsy on day 14. Patients with residual leukemia proceed to second remission induction therapy. Patients achieving complete remission (CR) proceed to intensification therapy. SECOND REMISSION INDUCTION THERAPY: Patients receive cytarabine IV over 120 hours on days 1-5 and daunorubicin hydrochloride IV and etoposide IV over 2 hours on days 1 and 2. Patients undergo bone marrow biopsy on day 42. Patients with residual leukemia are removed from the study. Patients achieving CR proceed to intensification therapy. INTENSIFICATION THERAPY: Patients are stratified and receive intensification therapy according to cytogenetic findings (favorable cytogenetics \[t(8;21)(q22q22), inv(16)(p13;q22), or t(16;16)(p13;q22) by cytogenetic and/or molecular analysis\] vs unfavorable cytogenetics \[all other cytogenetic findings, including normal cytogenetics\]). FAVORABLE CYTOGENETICS: Within 2-4 weeks after achieving CR, patients receive high-dose cytarabine IV over 3 hours twice daily on days 1, 3, and 5. Treatment repeats every 28 days for up to 3 courses. UNFAVORABLE CYTOGENETICS: Peripheral blood stem cell (PBSC) mobilization: Within 2-4 weeks after achieving CR, patients receive etoposide IV over 96 hours and high-dose cytarabine IV over 2 hours twice daily on days 1-4 and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 14 and continuing until blood counts recover. Patients then proceed to transplantation. PBSC OR BONE MARROW TRANSPLANTATION: Patients receive busulfan IV over 2 hours 4 times daily on days -7 to -4 and etoposide IV over 4 hours on day -3. Patients undergo autologous PBSC or bone marrow transplantation on day 0 and receive G-CSF SC once daily beginning on day 0 and continuing until blood counts recover. UNFAVORABLE CYTOGENETICS AND UNABLE TO UNDERGO PBSC TRANSPLANTATION: Within 2-4 weeks after achieving CR, patients receive etoposide, high-dose cytarabine, and G-CSF as in unfavorable cytogenetics (PBSC mobilization) followed by 2 courses of high-dose cytarabine as in favorable genetics. MAINTENANCE THERAPY: Within 60-90 days after completion of intensification therapy, patients receive decitabine IV over 1 hour on days 1-5. Treatment repeats every 6 weeks for up to 8 courses. After completion of study treatment, patients are followed up every 2 months for 1 year, every 6 months for 2 years, and then yearly for 2 years.

Conditions

Interventions

Type	Name	Description
PROCEDURE	Autologous Bone Marrow Transplantation	Undergo autologous bone marrow transplantation
PROCEDURE	Autologous Hematopoietic Stem Cell Transplantation	Undergo autologous PBSC transplantation
DRUG	Busulfan	Given IV
DRUG	Cytarabine	Given IV
DRUG	Daunorubicin Hydrochloride	Given IV
DRUG	Decitabine	Given IV
DRUG	Etoposide	Given IV
BIOLOGICAL	Filgrastim	Given SC
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies

Timeline

Start date: 2006-11-15
Primary completion: 2011-01-31
Completion: 2016-12-01
First posted: 2006-12-28
Last updated: 2019-02-19
Results posted: 2014-02-20

Locations

46 sites across 1 country: United States

Source: ClinicalTrials.gov record NCT00416598. Inclusion in this directory is not an endorsement.