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Acute Myeloid LeukemiaPhase 1/2NCT01222143

Safety and Efficacy Study of Nilotinib Combined With Mitoxantrone, Etoposide, and High-dose Cytarabine Induction Chemotherapy Followed by Consolidation for Patients With C-kit Positive Acute Myeloid Leukemia

A Phase 1/2 study testing NOVE-HiDAC and Nilotinib in people with Acute Myeloid Leukemia, run by University Health Network, Toronto at 1 site in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a phase I/II open-label study that is evaluating the toxicity and efficacy of nilotinib combined with mitoxantrone, etoposide, and high-dose cytarabine (NOVE-HiDAC) chemotherapy for patients with poor-risk acute myeloid leukemia (AML). There are two parts to the study. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
NOVE-HiDAC and Nilotinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteCanada
Study dates
Oct 2010to Apr 2015
Phase
Phase 1/2
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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • AML as defined by WHO (World Health Organization) criteria, all subtypes except APL (acute promyelocytic leukemia).
  • One of the following poor risk features:
  • Persistent leukemia (at least 10% bone marrow blasts) after induction therapy, consisting of cytarabine 100-200 mg/m2 plus an anthracycline.
  • Relapse within two years of achieving complete remission with such induction therapy. Any consolidation therapy is acceptable, including stem cell transplantation.
  • No prior inductions, but antecedent myeloproliferative disorder or CMML (chronic myelomonocytic leukemia) (These patients are given NOVE-HiDAC as frontline therapy at Princess Margaret Hospital).
  • Positivity for c-kit (CD117) in at least 30% of blasts as measured by flow cytometry. For relapsed patients, this will be assessed at the time of relapse. For primary induction failures the initial diagnostic sample may be used.
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  • Age 18-65.
  • ECOG performance status < 3 (see Appendix I).
  • Patients must have the following laboratory values within normal limits (WNL) at the local institution lab or corrected to WNL with supplements prior to first dose of study medication.
  • Potassium (WNL)
  • Magnesium (WNL)
  • No chemotherapy within the previous four weeks, other than hydroxyurea to control counts. Hydroxyurea may be continued up to Day 4 of treatment with nilotinib. If hydroxyurea is used, it must be stopped at least 48 hours prior to starting chemotherapy.
  • Able to give informed consent.

Who cannot join

  • Active uncontrolled infection.
  • Active CNS (central nervous system) leukemia
  • Serum creatinine > 200 umol/L.
  • Serum bilirubin > 1.5 x ULN, AST (aspartate aminotransferase) or ALT (alanine aminotransferase) > 2x ULN (upper limit of normal).
  • Serum amylase and lipase > 1.5x ULN
  • Left ventricular ejection fraction < 50%
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  • Impaired cardiac function including any of the following:
  • Long QT syndrome or a known family history of long QT syndrome
  • History or presence of clinically significant ventricular or atrial tachyarrhythmias
  • Clinically significant resting bradycardia (< 50 beats per minute)
  • Inability to monitor the QT interval by ECG
  • QTc > 450 msec on baseline ECG (electrocardiogram). If QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
  • Myocardial infarction within 1 year of starting study drug
  • Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
  • Patients currently receiving treatment with strong CYP3A4 inhibitors as listed in Section 5.8 and treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
  • Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
  • History of acute or chronic pancreatic disease.
  • Women who are pregnant, breast feeding, or of childbearing potential without a negative serum test at baseline. Male or female patients of childbearing potential unwilling to use contraceptive precautions throughout the trial and 3 months following discontinuation of study drug. Post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Women of childbearing potential must have a negative serum pregnancy test prior to the first dose of nilotinib.
  • Known hypersensitivity to study drugs or other components.

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: A Phase I/II Study Evaluating the Safety and Efficacy of Nilotinib Combined With Mitoxantrone, Etoposide, and High-Dose Cytarabine (NOVE-HiDAC) Induction Chemotherapy Followed by Consolidation Therapy for Poor-Risk Patients With C-kit Positive Acute Myeloid Leukemia (AML) up to Age 65

This is a phase I/II open-label study that is evaluating the toxicity and efficacy of nilotinib combined with mitoxantrone, etoposide, and high-dose cytarabine (NOVE-HiDAC) chemotherapy for patients with poor-risk acute myeloid leukemia (AML). There are two parts to the study. The first part (Phase I) will determine the maximum dose of nilotinib that can safely be given when combined with NOVE-HiDAC. This dose will then be used in combination with the NOVE-HiDAC regimen in the second part of the study (Phase II), which will evaluate the antileukemic activity of the treatment. The patients who achieve complete remission from the induction therapy (1 cycle) will then receive consolidation therapy combined with nilotinib (maximum of 2 cycles).

The patient population for this study will have AML and will fall into a poor risk category. This means they have persistent leukemia after induction therapy, they relapse within two years of achieving complete remission with induction therapy, or they have certain poor risk features at diagnosis. The AML cells will also be positive for c-kit (a stem cell factor receptor), which is involved in cancer cell growth. Nilotinib is a drug that blocks the effects of c-kit. Using this drug in combination with chemotherapy may improve ability of the chemotherapy drugs to kill leukemia cells. This may then increase the chances of the leukemia going into complete remission.

Being tested
NOVE-HiDAC, Nilotinib
Keywords
AML, NOVE-HiDAC, Nilotinib
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

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

  • NOVE-HiDACDrug

    NOVE-HiDAC consists of mitoxantrone, etoposide, and modified high-dose cytarabine. During induction patients will receive mitoxantrone by IV on Days 6-10, etoposide by IV on Days 6-10 and cytarabine by IV on Days 11-12.

    During consolidation patients will be receiving mitoxantrone by IV on Days 1-10 and cytarabine by IV on Days 6, 8 and 10.

  • NilotinibDrug

    The dose of nilotinib will be determined according to a dose escalation design. There will be three dose levels used in the study.

    During induction, nilotinib will be given orally on Days 1-12.

    During consolidation, nilotinib will be given orally on Days 1-10.

Study groups in NCT01222143
Study groupRoleWhat they receive
NOVE-HiDAC and NilotinibExperimentalAll patients will be receiving nilotinib combined with mitoxantrone, etoposide and high-dose cytarabine reinduction therapy. Patients achieving complete remission will receive consolidation therapy with nilotinib combined with high-dose cytarabine and mitoxantrone.
Receives: Drug: NOVE-HiDAC; Drug: Nilotinib

What is being measured

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

  1. To determine the maximum tolerated dose (MTD) of nilotinib when combined with the NOVE-HiDAC regimen (mitoxantrone, etoposide, and modified high-dose cytarabine).

    To determine the maximum tolerated dose (MTD) of nilotinib combined with mitoxantrone, etoposide, and modified high-dose cytarabine (NOVE-HiDAC) induction chemotherapy followed by consolidation chemotherapy for patients with poor risk c-kit positive AML.

    Measured: 2 years

  2. To evaluate the toxicity of the treatment regimen.

    Measured: 2 years

  3. To determine the complete response (CR) rate of this combination at the maximum tolerate dose (MTD) of nilotinib.

    Measured: 2 years

Secondary outcomes (5)

  1. To determine the disease-free survival of this combination.

    Measured: 2 years

  2. To evaluate the pharmacodynamic effects of nilotinib on pERK and pAKT (phosphorylated ERK and AKT) in AML cells in vivo.

    Measured: 2 years

  3. To correlate clinical responses with the degree of pAKT and pERK inhibition achieved in vivo.

    Measured: 2 years

  4. To correlate the degree of pAKT and pERK inhibition with nilotinib pharmacokinetics.

    Measured: 2 years

  5. To correlate pAKT and pERK inhibition with c-kit mutations.

    Measured: 2 years

Timeline

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

  1. First posted18 Oct 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionApr 2015
  4. Study completionApr 2015

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01222143
Sponsor's protocol ID
CAMN107YCA03T
Status last verified
Jun 2015
First submitted
13 Oct 2010
Last updated
22 Jun 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing NOVE-HiDAC and Nilotinib in people with Acute Myeloid Leukemia, run by University Health Network, Toronto at 1 site in Canada.

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

Who may be eligible to take part?

The sponsor lists 13 inclusion and 19 exclusion criteria. 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: stopped early, as of the sponsor's last update on 22 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was stopped early. Results are not available in the source record.

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?

To determine the maximum tolerated dose (MTD) of nilotinib when combined with the NOVE-HiDAC regimen (mitoxantrone, etoposide, and modified high-dose cytarabine). (time frame: 2 years). The study lists 3 primary outcomes in all. 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 NCT01222143.

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 22 Jun 2015.

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