LeukemiaPhase 3NCT00651261
Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
A Phase 3 study testing cytarabine, daunorubicin and midostaurin in people with Leukemia, run by Alliance for Clinical Trials in Oncology at 176 sites in 2 countries.
Trial summary
The purpose of this study is to compare the effects, good and/or bad, of a standard chemotherapy regimen for AML that includes the drugs daunorubicin and cytarabine combined with or without midostaurin (also known as PKC412), to find out which is better. Read more about this study
- Who is it for?
- Ages 18 to 59 years
- Conditions the study is for
- Leukemia
- What is being tested?
- cytarabine, daunorubicin and midostaurin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 717 participants
- Where
- 176 sitesin 2 countries
- Study dates
- Apr 2008to 28 Mar 2022
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 59 years
- All sexes
- No healthy volunteers
- Adult
- Documentation of Disease:
- Unequivocal diagnosis of AML ( > 20% blasts in the bone marrow based on the WHO classification), excluding M3 (acute promyelocytic leukemia). Patients with neurologic symptoms suggestive of CNS leukemia are recommended to have a lumbar puncture. Patients whose CSF is positive for AML blasts are not eligible.
- Documented FLT3 mutation (ITD or point mutation), determined by analysis in a protocol- designated FLT3 screening laboratory.
- Age Requirement:
- Age ≥ 18 and < 60 years
- Prior Therapy:
- No prior chemotherapy for leukemia or myelodysplasia with the following exceptions:
- emergency leukapheresis
- emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 5 days
- cranial RT for CNS leukostasis (one dose only)
- growth factor/cytokine support
- AML patients with a history of antecedent myelodysplasia (MDS) remain eligible for treatment on this trial, but must not have had prior cytotoxic therapy (e.g., azacitidine or decitabine)
- Patients who have developed therapy related AML after prior RT or chemotherapy for another cancer or disorder are not eligible.
- Cardiac Function: Patients with symptomatic congestive heart failure are not eligible.
- Initial Laboratory Value: Total bilirubin < 2.5 x ULN (Upper Limit of Normal)
- Pregnancy and Nursing Status:
- Non-pregnant and non-nursing due to the unknown teratogenic potential of midostaurin in humans, pregnant or nursing patients may not be enrolled.
- Women of childbearing potential must have a negative serum or urine pregnancy test within a sensitivity of at least 50 mIU/mL within 16 days prior to registration.
- Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or commit to TWO acceptable methods of birth control:
- one highly effective method (eg, IUD, hormonal (non-oral contraceptive), tubal ligation, or partner's vasectomy) and
- one additional effective method (e.g., latex condom, diaphragm or cervical cap)
- The two acceptable methods of birth control must be used AT THE SAME TIME, before beginning midostaurin/placebo therapy and continuing for 12 weeks after completion of all therapy.
- Note that oral contraceptives are not considered a high effective method because of the possibility of a drug interaction with midostaurin.
- Women of childbearing potential is defined as a sexually active mature woman who has not undergone a hysterectomy or who has not had menses at any time in the preceding 24 consecutive months.
- Men must agree not to father a child and must use a latex condom during any sexual contact with women of childbearing potential while taking midostaurin/placebo and for 12 weeks after therapy is stopped, even if they have undergone a successful vasectomy.
Trial locations and contacts
176 sites in 2 countries.
176 sites in 2 countries
United States170 sites
Summa Center for Cancer Care at Akron City Hospital
Akron, Ohio, 44309-2090
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87131-5636
Tulane Cancer Center Office of Clinical Research
Alexandria, Louisiana, 71315-3198
McFarland Clinic, PC
Ames, Iowa, 50010
MBCCOP - Medical College of Georgia Cancer Center
Augusta, Georgia, 30912
Aurora Presbyterian Hospital
Aurora, Colorado, 80012
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, 21201
Barberton Citizens Hospital
Barberton, Ohio, 44203
Battle Creek Health System Cancer Care Center
Battle Creek, Michigan, 49017
Mountainview Medical
Berlin Corners, Vermont, 05602
Mecosta County Medical Center
Big Rapids, Michigan, 49307
UAB Comprehensive Cancer Center
Birmingham, Alabama, 35294
Illinois CancerCare - Bloomington
Bloomington, Illinois, 61701
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Boston University Cancer Research Center
Boston, Massachusetts, 02118
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Boulder Community Hospital
Boulder, Colorado, 80301-9019
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001
Fletcher Allen Health Care - University Health Center Campus
Burlington, Vermont, 05401
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7295
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, 29425
West Virginia University Health Sciences Center - Charleston
Charleston, West Virginia, 25304
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, 28232-2861
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, 60611-3013
University of Illinois Cancer Center
Chicago, Illinois, 60612-7243
University of Chicago Cancer Research Center
Chicago, Illinois, 60637-1470
Marshfield Clinic - Chippewa Center
Chippewa Falls, Wisconsin, 54729
Charles M. Barrett Cancer Center at University Hospital
Cincinnati, Ohio, 45267
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado, 80933
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia, Missouri, 65203
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210-1240
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, 55433
Geisinger Cancer Institute at Geisinger Health
Danville, Pennsylvania, 17822-0001
Charles B. Eberhart Cancer Center at DeKalb Medical Center
Decatur, Georgia, 30033
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, 62526
St. Anthony Central Hospital
Denver, Colorado, 80204
Porter Adventist Hospital
Denver, Colorado, 80210
Presbyterian - St. Luke's Medical Center
Denver, Colorado, 80218
St. Joseph Hospital
Denver, Colorado, 80218
Rose Medical Center
Denver, Colorado, 80220
CCOP - Colorado Cancer Research Program
Denver, Colorado, 80224-2522
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Cancer Centers of the Carolinas - Easley
Easley, South Carolina, 29640
Center for Cancer Treatment & Prevention at Sacred Heart Hospital
Eau Claire, Wisconsin, 54701
Marshfield Clinic Cancer Care at Regional Cancer Center
Eau Claire, Wisconsin, 54701
Fairview Southdale Hospital
Edina, Minnesota, 55435
Swedish Medical Center
Englewood, Colorado, 80110
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, 46845
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, 55432
University of Florida Shands Cancer Center
Gainesville, Florida, 32610-0232
Butterworth Hospital at Spectrum Health
Grand Rapids, Michigan, 49503
CCOP - Grand Rapids
Grand Rapids, Michigan, 49503
Lacks Cancer Center at Saint Mary's Health Care
Grand Rapids, Michigan, 49503
North Colorado Medical Center
Greeley, Colorado, 80631
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, 54301-3526
Green Bay Oncology, Limited at St. Mary's Hospital
Green Bay, Wisconsin, 54303
St. Mary's Hospital Medical Center - Green Bay
Green Bay, Wisconsin, 54303
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, 54307-3508
Leo W. Jenkins Cancer Center at ECU Medical School
Greenville, North Carolina, 27834
Cancer Centers of the Carolinas - Faris Road
Greenville, South Carolina, 29605
Cancer Centers of the Carolinas - Grove Commons
Greenville, South Carolina, 29605
Greenville Hospital Cancer Center
Greenville, South Carolina, 29605
CCOP - Greenville
Greenville, South Carolina, 29615
Self Regional Cancer Center at Self Regional Medical Center
Greenwood, South Carolina, 29646
Cancer Centers of the Carolinas - Greer Medical Oncology
Greer, South Carolina, 29650
Helen and Harry Gray Cancer Center at Hartford Hospital
Hartford, Connecticut, 06102-5037
Geisinger Hazleton Cancer Center
Hazleton, Pennsylvania, 18201
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033-0850
Memorial Cancer Institute at Memorial Regional Hospital
Hollywood, Florida, 33021
Cancer Research Center of Hawaii
Honolulu, Hawaii, 96813
Queen's Cancer Institute at Queen's Medical Center
Honolulu, Hawaii, 96813
Baylor University Medical Center - Houston
Houston, Texas, 77030
Ben Taub General Hospital
Houston, Texas, 77030
Veterans Affairs Medical Center - Houston
Houston, Texas, 77030
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, 52242-1002
University of Mississippi Cancer Clinic
Jackson, Mississippi, 39216
Baptist Cancer Institute - Jacksonville
Jacksonville, Florida, 32207
Borgess Medical Center
Kalamazoo, Michigan, 49001
West Michigan Cancer Center
Kalamazoo, Michigan, 49007-3731
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Kinston Medical Specialists
Kinston, North Carolina, 28501
Monter Cancer Center of the North Shore-LIJ Health System
Lake Success, New York, 11042
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102
CCOP - Nevada Cancer Research Foundation
Las Vegas, Nevada, 89106
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109
Cleo Craig Cancer Research Clinic
Lawton, Oklahoma, 73505
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756-0002
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, 19958
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, 40536-0093
St. Rita's Medical Center
Lima, Ohio, 45801
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Sky Ridge Medical Center
Lone Tree, Colorado, 80124
Hope Cancer Care Center at Longmont United Hospital
Longmont, Colorado, 80501
McKee Medical Center
Loveland, Colorado, 80539
Medical Center of Central Georgia
Macon, Georgia, 31208
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, 53792-6164
CCOP - North Shore University Hospital
Manhasset, New York, 11030
Don Monti Comprehensive Cancer Center at North Shore University Hospital
Manhasset, New York, 11030
Holy Family Memorial Medical Center Cancer Care Center
Manitowoc, Wisconsin, 54221-1450
HealthEast Cancer Care at St. John's Hospital
Maplewood, Minnesota, 55109
Minnesota Oncology Hematology, PA - Maplewood
Maplewood, Minnesota, 55109
Bay Area Cancer Care Center at Bay Area Medical Center
Marinette, Wisconsin, 54143
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, 54449
Saint Joseph's Hospital
Marshfield, Wisconsin, 54449
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, 60153
University of Tennessee Cancer Institute - Memphis
Memphis, Tennessee, 38104
Tucker Center for Cancer Care at Orange Regional Medical Center
Middletown, New York, 10940-4199
Winthrop University Hospital
Mineola, New York, 11501
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, 55407
Hennepin County Medical Center - Minneapolis
Minneapolis, Minnesota, 55415
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
Marshfield Clinic - Lakeland Center
Minocqua, Wisconsin, 54548
Mary Babb Randolph Cancer Center at West Virginia University Hospitals
Morgantown, West Virginia, 26506
D.N. Greenwald Center
Mukwonago, Wisconsin, 53149
Tennessee Oncology, PLLC at Sarah Cannon Cancer Center
Nashville, Tennessee, 37203
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
Long Island Jewish Medical Center
New Hyde Park, New York, 11040
New York Weill Cornell Cancer Center at Cornell University
New York, New York, 10021
Mount Sinai Medical Center
New York, New York, 10029
CCOP - Christiana Care Health Services
Newark, Delaware, 19713
BroMenn Regional Medical Center
Normal, Illinois, 61761
Regional Cancer Center at Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, 53066
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, 73104
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, 68198-6805
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, 32803-1273
Oncology Hematology Associates of Central Illinois, PC - Peoria
Peoria, Illinois, 61615
Methodist Medical Center of Illinois
Peoria, Illinois, 61636
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224-1791
UPMC Cancer Centers
Pittsburgh, Pennsylvania, 15232
Ministry Medical Group at Saint Mary's Hospital
Rhinelander, Wisconsin, 54501
Marshfield Clinic - Indianhead Center
Rice Lake, Wisconsin, 54868
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, 23298-0037
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, 55422-2900
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, 14642
University of California Davis Cancer Center
Sacramento, California, 95817
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, 55416
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, 55416
Regions Hospital Cancer Care Center
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler
Savannah, Georgia, 31405
Cancer Centers of the Carolinas - Seneca
Seneca, South Carolina, 29672
Feist-Weiller Cancer Center at Louisiana State University Health Sciences
Shreveport, Louisiana, 71130-3932
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, 51101
Mercy Medical Center - Sioux City
Sioux City, Iowa, 51104
St. Luke's Regional Medical Center
Sioux City, Iowa, 51104
Avera Cancer Institute
Sioux Falls, South Dakota, 57105
Sanford Cancer Center at Sanford USD Medical Center
Sioux Falls, South Dakota, 57117-5039
Providence Cancer Institute at Providence Hospital - Southfield Campus
Southfield, Michigan, 48075
Cancer Centers of the Carolinas - Spartanburg
Spartanburg, South Carolina, 29307
Baystate Regional Cancer Program at D'Amour Center for Cancer Care
Springfield, Massachusetts, 01199
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St Louis, Missouri, 63110
Geisinger Medical Group - Scenery Park
State College, Pennsylvania, 16801
Marshfield Clinic at Saint Michael's Hospital
Stevens Point, Wisconsin, 54481
SUNY Upstate Medical University Hospital
Syracuse, New York, 13210
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, 33612-9497
North Suburban Medical Center
Thornton, Colorado, 80229
Munson Medical Center
Traverse City, Michigan, 49684
Ridgeview Medical Center
Waconia, Minnesota, 55387
Waukesha Memorial Hospital Regional Cancer Center
Waukesha, Wisconsin, 53188
Marshfield Clinic - Weston Center
Weston, Wisconsin, 54476
Ministry Saint Clare's Hospital
Weston, Wisconsin, 54476
Exempla Lutheran Medical Center
Wheat Ridge, Colorado, 80033
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
Wilkes-Barre, Pennsylvania, 18711
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157-1096
Marshfield Clinic - Wisconsin Rapids Center
Wisconsin Rapids, Wisconsin, 54494
Minnesota Oncology Hematology, PA - Woodbury
Woodbury, Minnesota, 55125
Metro Health Hospital
Wyoming, Michigan, 49519
Canada6 sites
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, T2N 4N2
Nova Scotia Cancer Centre
Halifax, Nova Scotia, B3H 1V8
Maisonneuve-Rosemont Hospital
Montreal, Quebec, H1T 2M4
McGill Cancer Centre at McGill University
Montreal, Quebec, H2W 1S6
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
About this study
Official title: A Phase III Randomized, Double-Blind Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy + Midostaurin (PKC412) (IND #101261) or Placebo in Newly Diagnosed Patients < 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia (AML)
The purpose of this study is to compare the effects, good and/or bad, of a standard chemotherapy regimen for AML that includes the drugs daunorubicin and cytarabine combined with or without midostaurin (also known as PKC412), to find out which is better. This research is being done because it is unknown whether the addition of midostaurin to chemotherapy treatment is better than chemotherapy treatment alone. Midostaurin has been tested in over 400 patients and is being studied in a number of illnesses, including AML, colon cancer, and lung cancer. Midostaurin blocks an enzyme, produced by a gene known as FLT3, that may have a role in the survival and growth of AML cells. Not all leukemia cells will have the abnormal FLT3 gene. This study will focus only on patients with leukemia cells with the abnormal FLT3 gene.
Read the detailed description
In this study, patients will receive either the experimental agent (midostaurin) or placebo combined with chemotherapy treatment. Patients are stratified according to FLT3 mutation status (internal tandem duplication [ITD] allelic ratio < 0.7 vs ITD allelic ratio ≥ 0.7 vs tandem kinase domain [TKD]). There are three parts to the study treatment: remission induction therapy, remission consolidation therapy and continuation therapy.
Remission Induction Therapy:
- Cytarabine 200 mg/m2/day by continuous intravenous infusion on days 1-7
- Daunorubicin 60 mg/m2/day by intravenous push or short infusion on days 1-3
- Midostaurin 50 mg (two 25 mg capsules) or placebo for midostaurin (2 capsules) twice a day by mouth on days 8-21
- A bone marrow aspiration will be performed in all patients on Day 21 to determine the need for a second induction cycle.
Remission Consolidation (Four Remission Consolidation Cycles):
- High dose cytarabine 3000 mg/m2 will be given by intravenous infusion over 3 hours every 12 hours on days 1, 3 and 5. Serial neurologic evaluation will be performed before and following the infusion of high-dose cytarabine.
- Dexamethasone 0.1% or other corticosteroid ophthalmic solution 2 drops to each eye once daily to begin 6-12 hours prior to the initiation of the cytarabine infusion and to continue for at least 24 hours after the last cytarabine dose.
- Midostaurin 50 mg (two 25 mg capsules) or placebo for midostaurin (2 capsules) twice a day by mouth on days 8-21
Midostaurin/Placebo Continuation Therapy:
- Midostaurin 50 mg (two 25 mg capsules) or placebo for midostaurin (2 capsules) by mouth twice a day for 28 days. Each cycle will be 28 days in length. Continuation therapy with midostaurin/placebo will continue until relapse or for 12 cycles maximum.
The primary and secondary objectives of this study are:
Primary objective:
- To determine if the addition of midostaurin to daunorubicin/cytarabine induction, high-dose cytarabine consolidation, and continuation therapy improves overall survival (OS) in both the mutant FLT3-ITD and FLT3-TKD AML patients
Secondary objectives:
- To compare the overall survival (OS) in the two groups using an analysis in which patients who receive a stem cell transplant are censored at the time of transplant
- To compare the complete response (CR) rate between the two treatment groups
- To compare the event-free survival (EFS) between the two treatment groups
- To compare the disease free survival (DFS) of the two treatment groups
- To compare the disease free survival rate one year after completion of the continuation phase of the two groups
- To assess the toxicity of the experimental combination
- To describe the interaction between treatment outcome and pretreatment characteristics such as age, performance status, white blood cell (WBC) count, morphology, cytogenetics, and molecular and pharmacodynamic features
- To assess the population pharmacokinetics (popPK) of midostaurin and its two major metabolites (CGP52421 and CGP62221). The potential association(s) between PK exposure and FLT3 status, OS, EFS and clinical response will be explored
There is a pharmacokinetic sub-study (CALGB 60706) within CALGB 10603. This embedded companion study must be offered to all patients enrolled on CALGB 10603, although patients may opt not to participate in CALGB 60706.
After study entry, patients are followed periodically for up to 10 years.
- Conditions
- Leukemia
- Being tested
- cytarabine, daunorubicin, midostaurin, placebo, dexamethasone acetate
- Keywords
- adult acute basophilic leukemia, adult acute eosinophilic leukemia, adult acute lymphoblastic 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), untreated adult acute myeloid leukemia
- Medical subject headings
- Leukemia, Leukemia, Basophilic, Acute, Leukemia, Eosinophilic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cytarabineDrug
Given IV
daunorubicinDrug
Given IV
midostaurinDrug
Given orally
placeboOther
Given orally
dexamethasone acetateDrug
ocular medication administration
| Study group | Role | What they receive |
|---|---|---|
| Induction and consolidation chemotherapy plus midostaurin | Experimental | Patients will receive a standard combination of chemotherapy drugs during remission induction therapy that includes cytarabine, daunorubicin, and the experimental drug midostaurin. Depending on the outcome of remission induction treatment, there may be a decision to discontinue the study treatment or a second remission induction cycle may be given. If remission induction therapy is successfully completed, patients will receive four courses of high-dose cytarabine consolidation chemotherapy plus dexamethasone together with the experimental drug midostaurin. All patients will undergo a bone marrow aspiration (and perhaps a biopsy) after the final course of remission consolidation chemotherapy. If the patient continues to respond to the treatment, the patient will receive continuation therapy with midostaurin for twelve (12) months. Receives: Drug: cytarabine; Drug: daunorubicin; Drug: midostaurin; Drug: dexamethasone acetate |
| Induction and consolidation chemotherapy plus placebo | Active comparator | Patients will receive a standard combination of chemotherapy drugs during remission induction therapy that includes cytarabine, daunorubicin, and placebo. Depending on the outcome of remission induction treatment, there may be a decision to discontinue the study treatment or a second remission induction cycle may be given. If remission induction therapy is successfully completed, patients will receive four courses of high-dose cytarabine consolidation chemotherapy plus dexamethasone together with placebo. All patients will undergo a bone marrow aspiration (and perhaps a biopsy) after the final course of remission consolidation chemotherapy. If the patient continues to respond to the treatment, the patient will receive continuation therapy with placebo for twelve (12) months. Receives: Drug: cytarabine; Drug: daunorubicin; Other: placebo; Drug: dexamethasone acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Overall survival (OS) was defined as the time interval from randomization to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.
Measured: Duration of study (Up to 10 years)
Secondary outcomes (5)
Event- Free Survival
Event free survival (EFS) was defined as the time from randomization until the earliest qualifying event, including: failure to obtain a CR on or before 60 days of initiation of protocol therapy; relapse; or death from any cause. Patients alive and event free at the time of analysis were censored on the date of last clinical assessment. The median EFS with 95% CI was estimated using the Kaplan-Meier method.
Due to a higher than expected transplant rate, EFS was promoted to be a key secondary endpoint.
Measured: Duration of study (Up to 10 years)
Overall Survival, Censoring Participants Who Receive a Stem Cell Transplant at the Time of the Transplant
Overall survival (OS) was defined as the time interval from randomization to death from any cause. Any participants who received a stem cell transplant were censored at the time of transplant. The median OS with 95% CI was estimated using the Kaplan-Meier method.
Measured: Duration of study (Up to 10 years)
Complete Response Rate
Percentage of participants who achieved a complete response (CR). A CR was defined as normalization of blood counts and a marrow showing less than 5% blasts occurring on or before day 60.
Measured: Induction therapy (up to 60 days)
Disease-free Survival (DFS)
Disease free survival (DFS) is defined as the time from documentation of first CR at any time to the first of relapse or death from any cause in participants who achieved a CR.
Measured: Duration of study (Up to 10 years)
DFS Rate One Year After Completing the Planned Continuation Phase
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2008 (estimated)
- Study startApr 2008
- Primary completionJul 2016
- Study completion28 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Alliance for Clinical Trials in OncologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 717 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alliance for Clinical Trials in Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Richard M. Stone, MD, Study chair, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00651261
- Sponsor's protocol ID
- CALGB-10603
- Other IDs
- CALGB-10603, EUDRACT-2006-006852-37, CDR0000590404
- Status last verified
- Sep 2026
- First submitted
- 1 Apr 2008
- Last updated
- 21 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Stone RM, Dohner H, Ehninger G, et al.: CALGB 10603 (RATIFY): A randomized phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3 mutated AML. [Abstract] J Clin Oncol 29 (Suppl 15): A-TPS199, 2011.
Seffernick AE, Mrozek K, Nicolet D, Stone RM, Eisfeld AK, Byrd JC, Archer KJ. High-dimensional genomic feature selection with the ordered stereotype logit model. Brief Bioinform. 2022 Nov 19;23(6):bbac414. doi: 10.1093/bib/bbac414.
PubMed 36184192Voso MT, Larson RA, Jones D, Marcucci G, Prior T, Krauter J, Heuser M, Lavorgna S, Nomdedeu J, Geyer SM, Walker A, Wei AH, Sierra J, Sanz MA, Brandwein JM, de Witte TM, Jansen JH, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Schlenk RF, Ganser A, Amadori S, Cheng Y, Chen Y, Pallaud C, Du L, Piciocchi A, Ehninger G, Byrd J, Thiede C, Dohner K, Stone RM, Dohner H, Bloomfield CD, Lo-Coco F. Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial. Blood Adv. 2020 Oct 13;4(19):4945-4954. doi: 10.1182/bloodadvances.2020002904.
PubMed 33049054Walker CJ, Kohlschmidt J, Eisfeld AK, Mrozek K, Liyanarachchi S, Song C, Nicolet D, Blachly JS, Bill M, Papaioannou D, Oakes CC, Giacopelli B, Genutis LK, Maharry SE, Orwick S, Archer KJ, Powell BL, Kolitz JE, Uy GL, Wang ES, Carroll AJ, Stone RM, Byrd JC, de la Chapelle A, Bloomfield CD. Genetic Characterization and Prognostic Relevance of Acquired Uniparental Disomies in Cytogenetically Normal Acute Myeloid Leukemia. Clin Cancer Res. 2019 Nov 1;25(21):6524-6531. doi: 10.1158/1078-0432.CCR-19-0725. Epub 2019 Aug 2.
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