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PKC412, Daunorubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: October 6, 2004
Last updated: March 9, 2015
Last verified: March 2015

RATIONALE: PKC412 may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It may also increase the effectiveness of daunorubicin and cytarabine by making cancer cells more sensitive to the drugs. Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining PKC412 with chemotherapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best way to give PKC412 when given either after or together with daunorubicin and cytarabine in treating patients with newly diagnosed acute myeloid leukemia.

Condition Intervention Phase
Acute Myeloid Leukemia (AML)
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: midostaurin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IB, Open-Label Study to Determine the Safety and Pharmacokinetics of Twice Daily Oral Dosing of PKC412 Administered in Combinations Sequentially and Concomitantly With Daunorubicin and Cytarabine for Standard Induction Therapy, and High Dose Cytarabine for Consolidation in Patients With Acute Myeloid Leukemia (AML)

Resource links provided by NLM:

Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Complete Response (CR) rate [ Time Frame: cycle 1, day 14, cycle day 21 - 28, end of each cycle ]
    cycle = between 28 days and 42 days in duration

Secondary Outcome Measures:
  • CR rate by FLT3 mutation and treatment arm [ Time Frame: CR:cycle 1, day 14, cycle day 21 - 28, end of each cycle, FLT3: monthly ]
  • Overall survival by FLT3 mutation status [ Time Frame: time of death of any cause(FLT# - minthly) ]

Enrollment: 69
Study Start Date: February 2004
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PKC412 administered sequentially
twice daily oral dosing of PKC412 administered sequentially
Drug: midostaurin
Other Name: PKC412
Experimental: PKC412 administered concomitantly
PKC412 administered concomitantly with standard induction daunorubicin and cytarabine therapy followed by high-dose consolidation therapy with cytarabine
Drug: cytarabine Drug: daunorubicin hydrochloride Drug: midostaurin
Other Name: PKC412

Detailed Description:



  • Determine the safety and tolerability of PKC412 administered sequentially or concurrently with induction chemotherapy comprising daunorubicin and cytarabine followed by consolidation therapy comprising high-dose cytarabine in patients with newly diagnosed acute myeloid leukemia.
  • Compare the pharmacokinetics of these regimens in these patients.


  • Determine the efficacy of these regimens, in terms of response rate, disease-free survival, and overall survival, in these patients.
  • Correlate genetic variation in drug metabolism genes, leukemia genes, and drug target genes with response in patients treated with these regimens.

OUTLINE: This is an open-label, multicenter study. Patients are alternately assigned to 1 of 2 induction treatment groups.

  • Induction therapy:

    • Group I (sequential therapy): Patients receive daunorubicin IV over 30 minutes on days 1-3, cytarabine IV continuously on days 1-7, and oral PKC412 twice daily on days 8-21 in the absence of disease progression or unacceptable toxicity.
    • Group II (concurrent therapy): Patients receive daunorubicin and cytarabine as in group I and oral PKC412 twice daily on days 1-7 and 15-21 in the absence of disease progression or unacceptable toxicity.

In both groups, patients are evaluated on day 28. Patients with persistent disease receive a second induction course comprising daunorubicin IV over 30 minutes on days 1 and 2, cytarabine IV continuously on days 1-5, and oral PKC412 on the same schedule as their assigned treatment group. Patients with a complete response after course 1 or course 2 proceed to consolidation therapy.

  • Consolidation therapy: Patients in both groups receive high-dose cytarabine IV over 3 hours twice daily on days 1, 3, and 5 and oral PKC412 on the same schedule as their assigned treatment group. Treatment repeats every 28-42 days for 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of consolidation therapy, patients in both groups continue to receive PKC412 alone, according to their assigned treatment group, every 28-42 days for up to 3 years in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed acute myeloid leukemia (AML)

    • Newly diagnosed disease
  • No history of or newly diagnosed myelodysplastic syndromes, history of myeloproliferative disease, or secondary AML
  • No CNS malignancy



  • 18 to 60

Performance status

  • Karnofsky 70-100%

Life expectancy

  • Not specified


  • Not specified


  • AST and ALT ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • No active viral hepatitis


  • Creatinine ≤ 1.5 times ULN
  • No chronic renal disease


  • Ejection fraction ≥ 50% by MUGA or echocardiogram
  • No congestive heart failure
  • No myocardial infarction within the past 6 months
  • No poorly controlled hypertension
  • No other cardiovascular disease


  • No pulmonary infiltrate, including those suspected to be infectious

    • Patients with pulmonary infection whose clinical symptoms have resolved are eligible provided there are no residual pulmonary infiltrates on chest x-ray


  • No gastrointestinal impairment or disease that would preclude absorption of study drugs
  • No uncontrolled diabetes
  • No active uncontrolled infection
  • No other disease, except carcinoma in situ, that would preclude study participation
  • No other severe or uncontrolled medical condition that would preclude study participation
  • HIV negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 3 months after study participation


Biologic therapy

  • At least 5 days since prior growth factors
  • No concurrent biological response modifiers


  • No prior chemotherapy
  • No other concurrent chemotherapy

Endocrine therapy

  • Not specified


  • No prior radiotherapy except radiation castration
  • No concurrent radiotherapy


  • More than 14 days since prior surgical procedure except central venous catheter placement or other minor procedure (e.g., skin biopsy)


  • More than 30 days since prior investigational agents
  • No other concurrent anticancer agents
  • No other concurrent investigational drugs
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Please refer to this study by its identifier: NCT00093600

United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
United States, Massachusetts
Dana Faber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-2014
United States, Texas
MD Anderson Cancer Center/University of Texas
Houston, Texas, United States, 77030
Novartis Investigative Site
Dresden, Germany
Novartis Investigative Site
Mainz, Germany
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Investigative Site, MD Novartis Investigative Site
  More Information

Responsible Party: Novartis Pharmaceuticals Identifier: NCT00093600     History of Changes
Other Study ID Numbers: NOVARTIS-CPKC412A2106
UCLA-0308139-01 ( Other Identifier: UCLA )
CDR0000389242 ( Other Identifier: PDQ (Physician Data Query) )
Study First Received: October 6, 2004
Last Updated: March 9, 2015

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
untreated adult acute myeloid leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Protein Kinase Inhibitors processed this record on May 25, 2017