A Randomized Phase III Study of Standard Cytarabine Plus Daunorubicin (7+3) Therapy or Idarubicin With High Dose Cytarabine (IA) Versus IA With Vorinostat (NSC-701852) (IA+V) in Younger Patients With Previously Untreated Acute Myeloid Leukemia (AML)
PRIMARY OBJECTIVES:
I. To compare event-free survival (EFS) between patients with acute myeloid leukemia (AML)
who receive standard 7+3 (cytarabine and daunorubicin hydrochloride) or idarubicin and
high-dose cytarabine (IA) to patients who receive IA + vorinostat. (Chemotherapy) II. To
determine whether it is possible to get 60% or more of adults with high-risk AML in first
complete remission (CR1) to allogeneic hematopoietic cell transplantation (HCT).
(Transplant)
SECONDARY OBJECTIVES:
I. To estimate the frequency and severity of toxicities of the three regimens in this
patient population. (Chemotherapy) II. To estimate disease-free survival (DFS) among
patients who receive transplant. (Transplant) III. To compare event-free survival (EFS)
between patients who receive standard 7+3 to patients who receive IA. (Chemotherapy) IV. To
estimate the prevalence of the mutations nucleophosmin (nucleolar phosphoprotein B23,
numatrin) (NPM1), isocitrate dehydrogenase 1 (NADP+), soluble (IDH1), isocitrate
dehydrogenase 2 (NADP+), mitochondrial (IDH2), tet methylcytosine dioxygenase 2 (TET2) and
DMT3A and the cytogenetic risk distribution of patients on this study and to evaluate the
association between these and overall survival (OS), EFS, DFS, and complete remission rate.
(Chemotherapy/Translational Medicine) V. To compare the complete response rate, DFS, and OS
between patients who receive standard 7+3 therapy or IA to patients who receive IA +
vorinostat. (Chemotherapy)
TERTIARY OBJECTIVES:
I. Future planned studies will include testing of histone H3 acetylation, induction of gamma
H2A histone family, member X (H2AX), analysis of reactive oxygen species (ROS) resistance
and deoxyribonucleic acid (DNA) methylation profiles. (Chemotherapy/Translational Medicine)
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
INDUCTION/RE-INDUCTION:
ARM I: Patients receive standard dose cytarabine intravenously (IV) continuously on days 1-7
and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive
re-induction treatment beginning on day 15. Patients achieving complete remission (CR) or
complete remission with incomplete platelet recover (CRi) may proceed to allogeneic
hematopoietic stem cell transplant (HSCT) or to consolidation therapy.
ARM II: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV
over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction
treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT
or to consolidation therapy.
ARM III: Patients receive vorinostat orally (PO) thrice daily (TID) on days 1-3, high-dose
cytarabine IV continuously on days 4-7, and idarubicin IV over 15 minutes on days 4-6.
Patients with residual blasts may receive re-induction treatment beginning on day 28.
Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy.
CONSOLIDATION:
ARM I: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5.
ARM II: Patients receive cytarabine IV continuously on days 1-3 and idarubicin IV over 15
minutes on days 1-2.
ARM III: Patients receive vorinostat PO TID on days 1-3, cytarabine IV continuously on days
4-6, and idarubicin IV over 15 minutes on days 4-5.
In all arms, treatment repeats every 28 days for 4 courses or until transplant in the
absence of disease progression or unacceptable toxicity.
TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or
consolidation therapy.
After completion of study treatment, patients are followed for every 3 months for 1 year,
every 6 months for 2 years, and then annually for 2 years.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
EFS
Up to 5 years
No
Guillermo Garcia-Manero
Principal Investigator
Southwest Oncology Group
United States: Food and Drug Administration
NCI-2013-00490
NCT01802333
February 2013
Name | Location |
---|---|
Cleveland Clinic Foundation | Cleveland, Ohio 44195 |
Washington University School of Medicine | Saint Louis, Missouri 63110 |
Loyola University Medical Center | Maywood, Illinois 60153 |
LDS Hospital | Salt Lake City, Utah 84143 |
Eastern Maine Medical Center | Bangor, Maine 04401 |
Via Christi Regional Medical Center | Wichita, Kansas 67214 |
Wesley Medical Center | Wichita, Kansas 67214 |
Great Falls Clinic | Great Falls, Montana 59405 |
Cancer Center of Kansas - Chanute | Chanute, Kansas 66720 |
Cancer Center of Kansas - Dodge City | Dodge City, Kansas 67801 |
Cancer Center of Kansas - Newton | Newton, Kansas 67114 |
Cancer Center of Kansas - Salina | Salina, Kansas 67042 |
Cancer Center of Kansas - Wellington | Wellington, Kansas 67152 |
Associates in Womens Health | Wichita, Kansas 67203 |
Cancer Center of Kansas - Winfield | Winfield, Kansas 67156 |
Bozeman Deaconess Hospital | Bozeman, Montana 59715 |
Kalispell Regional Medical Center | Kalispell, Montana 59901 |
American Fork Hospital | American Fork, Utah 84003 |
Logan Regional Hospital | Logan, Utah 84321 |
McKay-Dee Hospital Center | Ogden, Utah 84403 |
Welch Cancer Center | Sheridan, Wyoming 82801 |
Grandview Hospital | Dayton, Ohio 45405 |
Mountainview Medical | Berlin, Vermont 05602 |
Miami Valley Hospital | Dayton, Ohio 45409 |
Cancer Center of Kansas - Fort Scott | Fort Scott, Kansas 66701 |
Cancer Center of Kansas-Independence | Independence, Kansas 67301 |
Lawrence Memorial Hospital | Lawrence, Kansas 66044 |
Wayne Hospital | Greenville, Ohio 45331 |
Rocky Mountain Oncology | Casper, Wyoming 82609 |
Greene Memorial Hospital | Xenia, Ohio 45385 |
Harold Alfond Center for Cancer Care | Augusta, Maine 04330 |
Memorial Medical Center | Springfield, Illinois 62781 |
University of Alabama at Birmingham | Birmingham, Alabama 35294-3300 |
University of Rochester | Rochester, New York 14642 |
Wayne State University | Detroit, Michigan 48202 |
University of Arizona Health Sciences Center | Tucson, Arizona 85724 |
Cancer Center of Kansas - McPherson | McPherson, Kansas 67460 |
University Of Vermont | Burlington,, Vermont 05403 |
University of Kentucky | Lexington, Kentucky 40536-0098 |
Wichita CCOP | Wichita, Kansas 67214-3882 |
Montana Cancer Consortium CCOP | Billings, Montana 59101 |
Decatur Memorial Hospital | Decatur, Illinois 62526 |
Montana Cancer Specialists | Missoula, Montana 59807-7877 |
Reid Hospital and Health Care Services | Richmond, Indiana 47374 |
Mercy Medical Center-Sioux City | Sioux City, Iowa 51104 |
Saint Luke's Regional Medical Center | Sioux City, Iowa 51104 |
Cancer Center of Kansas - El Dorado | El Dorado, Kansas 67042 |
Cancer Center of Kansas-Kingman | Kingman, Kansas 67068 |
Cancer Center of Kansas - Parsons | Parsons, Kansas 67357 |
Cancer Center of Kansas - Pratt | Pratt, Kansas 67124 |
Cancer Center of Kansas-Wichita Medical Arts Tower | Wichita, Kansas 67208 |
Cancer Center of Kansas - Main Office | Wichita, Kansas 67214 |
Hematology-Oncology Centers of the Northern Rockies PC | Billings, Montana 59101 |
Saint Vincent Healthcare | Billings, Montana 59101 |
Billings Clinic | Billings, Montana 59107-7000 |
Saint James Community Hospital and Cancer Treatment Center | Butte, Montana 59701 |
Benefis Healthcare- Sletten Cancer Institute | Great Falls, Montana 59405 |
Saint Peter's Community Hospital | Helena, Montana 59601 |
Saint Patrick Hospital - Community Hospital | Missoula, Montana 59802 |
Kinston Medical Specialists PA | Kinston, North Carolina 28501 |
Summa Barberton Hospital | Barberton, Ohio 44203 |
Good Samaritan Hospital - Dayton | Dayton, Ohio 45406 |
Dayton CCOP | Dayton, Ohio 45429 |
Samaritan North Health Center | Dayton, Ohio 45415 |
Blanchard Valley Hospital | Findlay, Ohio 45840 |
Atrium Medical Center-Middletown Regional Hospital | Franklin, Ohio 45005-1066 |
Kettering Medical Center | Kettering, Ohio 45429 |
Upper Valley Medical Center | Troy, Ohio 45373 |
Cancer Center of Kansas-Liberal | Liberal, Kansas 67901 |
Sandra L Maxwell Cancer Center | Cedar City, Utah 84720 |
Intermountain Medical Center | Murray, Utah 84157 |
Utah Valley Regional Medical Center | Provo, Utah 84603 |
Dixie Medical Center Regional Cancer Center | Saint George, Utah 84770 |
Utah Cancer Specialists-Salt Lake City | Salt Lake City, Utah 84106 |
Arizona Cancer Center at University Medical Center North | Tucson, Arizona 85719 |
Stanford University Hospitals and Clinics | Stanford, California 94305 |
Siouxland Hematology Oncology Associates | Sioux City, Iowa 51101 |
Summa Akron City Hospital | Akron, Ohio 44304 |
Franciscan St. Francis Health | Indianapolis, Indiana 46237 |
Southwest Oncology Group | San Antonio, Texas 78245 |