Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT00651261|
Recruitment Status : Active, not recruiting
First Posted : April 2, 2008
Results First Posted : February 6, 2017
Last Update Posted : August 18, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Leukemia||Drug: cytarabine Drug: daunorubicin Drug: midostaurin Other: placebo Drug: dexamethasone acetate||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||717 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|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)|
|Actual Study Start Date :||April 2008|
|Actual Primary Completion Date :||July 2016|
Experimental: Induction and consolidation chemotherapy plus midostaurin
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.
Drug: dexamethasone acetate
ocular medication administration
Active Comparator: Induction and consolidation chemotherapy plus placebo
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.
Drug: dexamethasone acetate
ocular medication administration
- Overall Survival (OS) [ Time Frame: Duration of study (Up to 10 years) ]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.
- Event- Free Survival [ Time Frame: Duration of study (Up to 10 years) ]
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.
- Overall Survival, Censoring Participants Who Receive a Stem Cell Transplant at the Time of the Transplant [ Time Frame: Duration of study (Up to 10 years) ]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.
- Complete Response Rate [ Time Frame: Induction therapy (up to 60 days) ]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.
- Disease-free Survival (DFS) [ Time Frame: Duration of study (Up to 10 years) ]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.
- DFS Rate One Year After Completing the Planned Continuation Phase [ Time Frame: 30 months ]
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|Ages Eligible for Study:||18 Years to 59 Years (Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
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 ≥ 18 and < 60 years
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.
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): NCT00651261
|Study Chair:||Richard M. Stone, MD||Dana-Farber Cancer Institute|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Alliance for Clinical Trials in Oncology|
|Other Study ID Numbers:||
CDR0000590404 ( Registry Identifier: Phyisician Data Query )
|First Posted:||April 2, 2008 Key Record Dates|
|Results First Posted:||February 6, 2017|
|Last Update Posted:||August 18, 2021|
|Last Verified:||August 2021|
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Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
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