Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia - Full Text View

Purpose

RATIONALE: Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Midostaurin may help daunorubicin and cytarabine work better by making cancer cells more sensitive to the drugs. Midostaurin also may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective with or without midostaurin in treating acute myeloid leukemia.

PURPOSE: This randomized phase III trial is studying giving daunorubicin and cytarabine with or without midostaurin followed by high-dose cytarabine and midostaurin to see how well it works in treating patients with newly diagnosed acute myeloid leukemia.

Condition	Intervention	Phase
Leukemia	Drug: cytarabine Drug: daunorubicin hydrochloride Drug: midostaurin Other: placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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)

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia

Drug Information available for: Cytarabine Daunorubicin Daunorubicin hydrochloride Daunorubicin citrate

U.S. FDA Resources

Further study details as provided by Alliance for Clinical Oncology Trials:

Primary Outcome Measures:

Overall survival (OS) [ Time Frame: Duration of study (Up to 10 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

OS where patients who receive a stem cell transplant are censored at the time of the transplant [ Time Frame: Duration of study (Up to 10 years) ] [ Designated as safety issue: No ]
Complete response rate in the remission induction stage of the study [ Time Frame: Duration of study (Up to 10 years) ] [ Designated as safety issue: No ]
Event- free survival [ Time Frame: Duration of study (Up to 10 years) ] [ Designated as safety issue: Yes ]
Disease-free survival (DFS) [ Time Frame: Duration of study (Up to 10 years) ] [ Designated as safety issue: No ]
DFS rate one year after completing the planned continuation phase [ Time Frame: 30 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	714
Study Start Date:	April 2008
Estimated Primary Completion Date:	July 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm I Patients receive remission induction comprising cytarabine IV continuously on days 1-7, daunorubicin hydrochloride IV on days 1-3, and oral midostaurin twice daily on days 8-21. Some patients may receive a second course of remission induction beginning on or after day 24. Beginning at least 4 weeks after remission induction, patients with a complete response (CR) receive consolidation therapy comprising high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5 and oral midostaurin twice daily on days 8-21. Consolidation therapy repeats every 4 weeks for up to 4 courses. Beginning at least 14 days after consolidation therapy, patients who remain in CR receive continuation therapy comprising oral midostaurin twice daily on days 1-14. Continuation therapy repeats every 28 days for up to 12 months.	Drug: cytarabine Given IV Drug: daunorubicin hydrochloride Given IV Drug: midostaurin Given orally
Active Comparator: Arm II Patients receive remission induction comprising cytarabine and daunorubicin hydrochloride as in arm I and oral placebo twice daily on days 8-21. Some patients may receive a second course of remission induction beginning on or after day 24. Beginning at least 4 weeks after remission induction, patients with a CR receive consolidation therapy comprising high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5 and oral placebo twice daily on days 8-21. Consolidation therapy repeats every 4 weeks for up to 4 courses. Beginning at least 14 days after consolidation therapy, patients who remain in CR receive continuation therapy comprising oral placebo twice daily on days 1-28. Continuation therapy repeats every 28 days for up to 12 months.	Drug: cytarabine Given IV Drug: daunorubicin hydrochloride Given IV Other: placebo Given orally

Arms

Assigned Interventions

Experimental: Arm I

Patients receive remission induction comprising cytarabine IV continuously on days 1-7, daunorubicin hydrochloride IV on days 1-3, and oral midostaurin twice daily on days 8-21. Some patients may receive a second course of remission induction beginning on or after day 24. Beginning at least 4 weeks after remission induction, patients with a complete response (CR) receive consolidation therapy comprising high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5 and oral midostaurin twice daily on days 8-21. Consolidation therapy repeats every 4 weeks for up to 4 courses. Beginning at least 14 days after consolidation therapy, patients who remain in CR receive continuation therapy comprising oral midostaurin twice daily on days 1-14. Continuation therapy repeats every 28 days for up to 12 months.

Drug: cytarabine

Given IV

Drug: daunorubicin hydrochloride

Given IV

Drug: midostaurin

Given orally

Active Comparator: Arm II

Patients receive remission induction comprising cytarabine and daunorubicin hydrochloride as in arm I and oral placebo twice daily on days 8-21. Some patients may receive a second course of remission induction beginning on or after day 24. Beginning at least 4 weeks after remission induction, patients with a CR receive consolidation therapy comprising high-dose cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5 and oral placebo twice daily on days 8-21. Consolidation therapy repeats every 4 weeks for up to 4 courses. Beginning at least 14 days after consolidation therapy, patients who remain in CR receive continuation therapy comprising oral placebo twice daily on days 1-28. Continuation therapy repeats every 28 days for up to 12 months.

Drug: cytarabine

Given IV

Drug: daunorubicin hydrochloride

Given IV

Other: placebo

Given orally

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 59 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Unequivocal diagnosis of acute myeloid leukemia (AML) meeting the following criteria:
- More than 20% blasts present in the bone marrow, as defined by WHO classification
- Documented FLT3 mutation (i.e., internal tandem duplication [ITD] or point mutation), determined by analysis in a protocol-designated FLT3 screening laboratory
No acute promyelocytic leukemia (M3)
Patients with antecedent myelodysplasia (MDS) allowed, provided they received no prior cytotoxic (including azacytidine or decitabine) therapy for MDS
No therapy-related AML after prior radiotherapy or chemotherapy for another disorder or cancer
Patients with neurologic symptoms suggestive of CNS leukemia may undergo a lumbar puncture
- Patients with a positive CSF for AML blasts are not eligible

PATIENT CHARACTERISTICS:

No symptomatic congestive heart failure
Total bilirubin < 2.5 times upper limit of normal
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use 2 methods of effective contraception during and for 12 weeks after completion of study therapy

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior therapy for leukemia or myelodysplasia, except for the following:
- Emergency leukapheresis
- Emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 5 days
- Cranial radiotherapy for CNS leukostasis (one dose only)
- Growth factor or cytokine support
No concurrent hormones or other chemotherapy, except steroids given for hypersensitivity or transfusion reactions or hormones for non-disease-related conditions (e.g., insulin for diabetes)
No concurrent apprepitant
No concurrent enrollment on another clinical trial with investigational agents

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00651261

Show 176 Study Locations

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Richard M. Stone, MD

Dana-Farber Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Alliance for Clinical Oncology Trials ( Cancer and Leukemia Group B )
ClinicalTrials.gov Identifier:	NCT00651261 History of Changes
Other Study ID Numbers:	CDR0000590404, CALGB-10603, EUDRACT-2006-006852-37
Study First Received:	April 1, 2008
Last Updated:	April 4, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Oncology Trials:

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

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
4'-N-benzoylstaurosporine
Daunorubicin
Staurosporine
Antimetabolites, Antineoplastic
Antimetabolites

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 19, 2013