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Phase II Study of Maintenance Therapy With Decitabine (NSC #127716, IND #50733) Following Standard Induction and Cytogenetic Risk-Adapted Intensification in Previously Untreated Patients With AML < 60 Years


Phase 2
15 Years
59 Years
Open (Enrolling)
Both
Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), 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

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Trial Information

Phase II Study of Maintenance Therapy With Decitabine (NSC #127716, IND #50733) Following Standard Induction and Cytogenetic Risk-Adapted Intensification in Previously Untreated Patients With AML < 60 Years


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 AML who achieve and
maintain first 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 DNA demethylation including downregulation of 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 CBF or non-CBF AML.

V. To continue the investigation begun in CALGB 19808 aimed at correlation of the rate of
relapse and toxicity with 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 CR, DFS, EFS, and OS, with pretreatment
characteristics such as age, sex, race, blood counts, morphology, immunophenotype,
cytogenetics, and molecular features of AML.

OUTLINE: This is a multicenter study.

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.

Blood and bone marrow samples are obtained periodically during study therapy for cytogenetic
analysis.

After completion of study treatment, patients are followed up every 2 month for 1 year,
every 6 months for 3 years, and then at 1 year.


Inclusion Criteria:



- Histologically confirmed acute myeloid leukemia (AML)

- More than 20% blasts in the bone marrow

- Antecedent myelodysplasia allowed provided there is no bone marrow biopsy
showing myelodysplastic syndromes more than 3 months prior to study entry

- Therapy-related AML allowed provided patient has not had primary disease or
received chemotherapy within the past 2 years

- No M3 disease (acute promyelocytic leukemia)

- Registered on CALGB-8461 and CALGB-20602

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No prior azacitidine or decitabine

- No prior treatment for leukemia or myelodysplastic syndromes, except in the following
circumstances:

- Emergency leukapheresis

- Emergency treatment for hyperleukocytosis with hydroxyurea

- Cranial radiation therapy for CNS leukostasis (one dose only)

- Growth factor/cytokine support

- No other concurrent chemotherapy

- No concurrent hormonal therapy except steroids for nausea, adrenal failure, or septic
shock or hormones administered for nondisease-related conditions

- No concurrent palliative radiation therapy

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Feasibility of maintenance decitabine administered to patients following intensive induction and consolidation chemotherapy, with or without autologous PSCT

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

William Blum

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00444

NCT ID:

NCT00416598

Start Date:

November 2006

Completion Date:

Related Keywords:

  • Adult Acute Basophilic Leukemia
  • Adult Acute Eosinophilic Leukemia
  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
  • 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
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Basophilic, Acute
  • Leukemia, Eosinophilic, Acute
  • Leukemia, Erythroblastic, Acute
  • Leukemia, Megakaryoblastic, Acute
  • Leukemia, Monocytic, Acute
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelomonocytic, Acute
  • Leukemia, Myelomonocytic, Chronic
  • Hypereosinophilic Syndrome

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Washington University School of MedicineSaint Louis, Missouri  63110
Rhode Island HospitalProvidence, Rhode Island  02903
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Western Pennsylvania HospitalPittsburgh, Pennsylvania  15224
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
North Shore University HospitalManhasset, New York  11030
Eastern Maine Medical CenterBangor, Maine  04401
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Mount Sinai Medical CenterNew York, New York  10029
Brigham and Women's HospitalBoston, Massachusetts  02115
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240
Beebe Medical CenterLewes, Delaware  19958
Mountainview MedicalBerlin, Vermont  05602
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Miriam HospitalProvidence, Rhode Island  02906
University of North CarolinaChapel Hill, North Carolina  27599
Blood and Marrow Transplant Group of GeorgiaAtlanta, Georgia  30342-1601
Dartmouth Hitchcock Medical CenterLebanon, New Hampshire  03756
University Of VermontBurlington,, Vermont  05403
Florida HospitalOrlando, Florida  32803
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
University of California San Francisco Medical Center-Mount ZionSan Francisco, California  94115
Fort Wayne Medical Oncology and Hematology Inc - State BoulevardFort Wayne, Indiana  46845
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
Cheshire Medical Center-Dartmouth-Hitchcock KeeneKeene, New Hampshire  03431
Cooper Hospital University Medical CenterCamden, New Jersey  08103
State University of New York Upstate Medical UniversitySyracuse, New York  13210
University of Maryland Greenebaum Cancer CenterBaltimore, Maryland  21201
University of IllinoisChicago, Illinois  60612
Commonwealth Hematology Oncology PC-WorcesterWorcester, Massachusetts  01605
University of Missouri - Ellis FischelColumbia, Missouri  65203
Veterans AdministrationColumbia, Missouri  65201
Monter Cancer CenterLake Success, New York  11042
North Shore-LIJ Health System CCOPManhasset, New York  11030
Christiana Care Health System-Christiana HospitalNewark, Delaware  19718