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

NCT ID: NCT00093600

Last Updated: 2020-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

69 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-02-29

Study Completion Date

2011-06-30

Brief Summary

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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.

Detailed Description

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OBJECTIVES:

Primary

* 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.

Secondary

* 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.

Conditions

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Acute Myeloid Leukemia (AML)

Keywords

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PKC412 administered sequentially

twice daily oral dosing of PKC412 administered sequentially

Group Type EXPERIMENTAL

midostaurin

Intervention Type DRUG

PKC412 administered concomitantly

PKC412 administered concomitantly with standard induction daunorubicin and cytarabine therapy followed by high-dose consolidation therapy with cytarabine

Group Type EXPERIMENTAL

cytarabine

Intervention Type DRUG

daunorubicin hydrochloride

Intervention Type DRUG

midostaurin

Intervention Type DRUG

Interventions

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cytarabine

Intervention Type DRUG

daunorubicin hydrochloride

Intervention Type DRUG

midostaurin

Intervention Type DRUG

Other Intervention Names

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PKC412

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Investigative Site, MD

Role: STUDY_DIRECTOR

Novartis Investigative Site

Locations

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Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States

Site Status

Dana Faber Cancer Institute

Boston, Massachusetts, United States

Site Status

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

MD Anderson Cancer Center/University of Texas

Houston, Texas, United States

Site Status

Novartis Investigative Site

Dresden, , Germany

Site Status

Novartis Investigative Site

Mainz, , Germany

Site Status

Countries

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United States Germany

References

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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.

Reference Type RESULT
PMID: 22627678 (View on PubMed)

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=14505

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

Other Identifiers

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UCLA-0308139-01

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000389242

Identifier Type: OTHER

Identifier Source: secondary_id

NOVARTIS-CPKC412A2106

Identifier Type: -

Identifier Source: org_study_id