Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology ( Cancer and Leukemia Group B )
ClinicalTrials.gov Identifier:
NCT00651261
First received: April 1, 2008
Last updated: April 4, 2013
Last verified: October 2011
  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:


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

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

  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
Investigators
Principal Investigator: Richard M. Stone, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology ( 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 Trials in Oncology:
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 April 22, 2014