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

NCT00093600 | Completed Phase 1

• 3 other identifiers: NOVARTIS-CPKC412A2106UCLA-0308139-01CDR0000389242
• Study Type: interventional
• Target: 69
• Locations: 2 countries
• Sites: 6

Brief Summary

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.

Conditions

Acute Myeloid Leukemia (AML)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) rate

  cycle = between 28 days and 42 days in duration

  cycle 1, day 14, cycle day 21 - 28, end of each cycle

Secondary Outcomes (2)

• CR rate by FLT3 mutation and treatment arm

  CR:cycle 1, day 14, cycle day 21 - 28, end of each cycle, FLT3: monthly

• Overall survival by FLT3 mutation status

  time of death of any cause(FLT# - minthly)

Study Arms (2)

PKC412 administered sequentially

EXPERIMENTAL

twice daily oral dosing of PKC412 administered sequentially

Drug: midostaurin

PKC412 administered concomitantly

EXPERIMENTAL

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

Interventions

cytarabine DRUG

PKC412 administered concomitantly

daunorubicin hydrochloride DRUG

PKC412 administered concomitantly

midostaurin DRUG

Also known as: PKC412

PKC412 administered concomitantly; PKC412 administered sequentially

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

DISEASE CHARACTERISTICS: * 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 PATIENT CHARACTERISTICS: Age * 18 to 60 Performance status * Karnofsky 70-100% Life expectancy * Not specified Hematopoietic * Not specified Hepatic * AST and ALT ≤ 1.5 times upper limit of normal (ULN) * Bilirubin ≤ 1.5 times ULN * No active viral hepatitis Renal * Creatinine ≤ 1.5 times ULN * No chronic renal disease Cardiovascular * 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 Pulmonary * 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 Other * 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 PRIOR CONCURRENT THERAPY: Biologic therapy * At least 5 days since prior growth factors * No concurrent biological response modifiers Chemotherapy * No prior chemotherapy * No other concurrent chemotherapy Endocrine therapy * Not specified Radiotherapy * No prior radiotherapy except radiation castration * No concurrent radiotherapy Surgery * More than 14 days since prior surgical procedure except central venous catheter placement or other minor procedure (e.g., skin biopsy) Other * More than 30 days since prior investigational agents * No other concurrent anticancer agents * No other concurrent investigational drugs

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

Dana Faber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201-2014, United States

Location

MD Anderson Cancer Center/University of Texas

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Dresden, Germany

Location

Novartis Investigative Site

Mainz, Germany

Location

Related Publications (1)

• Stone RM, Fischer T, Paquette R, Schiller G, Schiffer CA, Ehninger G, Cortes J, Kantarjian HM, DeAngelo DJ, Huntsman-Labed A, Dutreix C, del Corral A, Giles F. Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia. Leukemia. 2012 Sep;26(9):2061-8. doi: 10.1038/leu.2012.115. Epub 2012 Apr 27.

  PMID: 22627678 RESULT

Related Links

• Results for CPKC412A2106 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Congenital Abnormalities

Interventions

Cytarabine; Daunorubicin; midostaurin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Novartis Investigative Site, MD

  Novartis Investigative Site

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2004
• First Posted: October 8, 2004
• Study Start: February 1, 2004
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: December 19, 2020

Record last verified: 2015-03

Locations

US (4); DE (2)