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AzTrials

Acute Myeloid Leukemia (AML)Phase 1NCT00093600

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

A Phase 1 study testing cytarabine, daunorubicin hydrochloride and midostaurin in people with Acute Myeloid Leukemia (AML), run by Novartis Pharmaceuticals at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Acute Myeloid Leukemia (AML)
What is being tested?
cytarabine, daunorubicin hydrochloride and midostaurin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
69 participants
Where
6 sitesin 2 countries
Study dates
Feb 2004to Jun 2011
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

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

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United States4 sites

  • Dana Faber Cancer Institute

    Boston, Massachusetts, 02115

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201-2014

  • MD Anderson Cancer Center/University of Texas

    Houston, Texas, 77030

  • Jonsson Comprehensive Cancer Center at UCLA

    Los Angeles, California, 90095-1781

Other trials in United States

Germany2 sites

  • Novartis Investigative Site

    Dresden

  • Novartis Investigative Site

    Mainz

Other trials in Germany

About this study

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)

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.

Read the detailed description

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.

Being tested
cytarabine, daunorubicin hydrochloride, midostaurin
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
Medical subject headings
Leukemia, Myeloid, Acute, Congenital Abnormalities

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cytarabineDrug

  • daunorubicin hydrochlorideDrug

  • midostaurinDrug

    Also called PKC412

Study groups in NCT00093600
Study groupRoleWhat they receive
PKC412 administered sequentiallyExperimentaltwice daily oral dosing of PKC412 administered sequentially
Receives: Drug: midostaurin
PKC412 administered concomitantlyExperimentalPKC412 administered concomitantly with standard induction daunorubicin and cytarabine therapy followed by high-dose consolidation therapy with cytarabine
Receives: Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: midostaurin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete Response (CR) rate

    cycle = between 28 days and 42 days in duration

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

Secondary outcomes (2)

  1. CR rate by FLT3 mutation and treatment arm

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

  2. Overall survival by FLT3 mutation status

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Oct 2004 (estimated)
  2. Study startFeb 2004
  3. Primary completionJun 2011
  4. Study completionJun 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00093600
Sponsor's protocol ID
NOVARTIS-CPKC412A2106
Other IDs
UCLA-0308139-01, CDR0000389242
Status last verified
Mar 2015
First submitted
6 Oct 2004
Last updated
19 Dec 2020
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 22627678

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing cytarabine, daunorubicin hydrochloride and midostaurin in people with Acute Myeloid Leukemia (AML), run by Novartis Pharmaceuticals at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response (CR) rate (time frame: cycle 1, day 14, cycle day 21 - 28, end of each cycle). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00093600, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2020.

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